PROVISIONAL
TRANSLATION

National Action Plan on
Antimicrobial Resistance (AMR)
2023-2027

April 7, 2023
The Government of Japan*The translation in this document is to be considered solely as a reference. In the event of any conflict orinconsistency between the Japanese and English versions, the original Japanese version shall prevail.

CONTENTS
Contents ............................................................................................................................................................................... 2
Introduction......................................................................................................................................................................... 4
Abbreviations ...................................................................................................................................................................... 6
The Efforts and Results of the National Action Plan on Antimicrobial Resistance (AMR) (2016-2020) .................... 8
The Current State and Challenges of Antimicrobial Resistance in Japan ................................................................... 11
National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) ...................................................................... 18
Goal 1 Improve Public Awareness and Understanding, and Promote Education and Training of Professionals ... 22
Strategy 1.1

Promote Public Awareness-Raising Activities to Improve Public Knowledge and Understandingof AMR ................................................................................................................................................... 23

Strategy 1.2

Promote Education and Training on AMR of Professionals Involved in Related Fields ........................ 26

Goal 2 Continuously Monitor Antimicrobial Resistance and Use of Antimicrobials, and Appropriately Understandthe Signs of Change and Spread of Antimicrobial Resistance ...................................................................................... 30
Strategy 2.1

Strengthen the Surveillance of Antimicrobial Resistance in Healthcare and Nursing Care ................... 31

Strategy 2.2

Monitor the Trend of the Antimicrobial Use at Medical Institutions ..................................................... 35

Strategy 2.3

Strengthen Antimicrobial Resistance Surveillance in the Fields of Veterinary Medicine,Livestock and Aquaculture ..................................................................................................................... 38

Strategy 2.4

Standardize Methods of Laboratory Testing and Strengthen Testing Functions of Antimicrobial
Resistance at Clinical, Commercial and Public Health Laboratories ...................................................... 40

Strategy 2.5

Implement Integrated One Health Surveillance Including Humans, Animals, Food, and theEnvironment ........................................................................................................................................... 42

Goal 3 Prevent the Spread of Antimicrobial-Resistant Organisms by Implementing Appropriate Infection
Prevention and Control .................................................................................................................................................... 45
Strategy 3.1

Infection Prevention and Control in Healthcare and Nursing Care and Promotion of Regional
Cooperation ............................................................................................................................................ 46

Strategy 3.2

Promote Infection Prevention and Control in Livestock and Aquaculture, Veterinary Medicine
and Food Chain ....................................................................................................................................... 48

Strategy 3.3

Strengthen the Outbreak Response Capacity against Antimicrobial-Resistant Infections ...................... 50

Goal 4 Promote Appropriate Use of Antimicrobials in the Fields of Healthcare, Livestock and Aquaculture ........ 53
Strategy 4.1

Promote Antimicrobial Stewardship at Medical Institutions .................................................................. 54

Strategy 4.2

Ensure Prudent Use of Antibiotics for Animals in the Field of Livestock and Aquaculture andVeterinary Medicine ............................................................................................................................... 57

Goal 5 Promote Research on Antimicrobial Resistance and Foster Research and Development and Other
Measures to Secure the Means to Prevent, Diagnose and Treat the Antimicrobial-Resistant Infections ................. 60
Strategy 5.1

Promote Research to Elucidate the Mechanism of the Emergence and Transmission of
Antimicrobial Resistance and Its Socioeconomic Impact ....................................................................... 61

Strategy 5.2

Promote Research on Public Awareness/Education on Antimicrobial Resistance, Infection
Prevention and Control, and Antimicrobial Stewardship ....................................................................... 64

Strategy 5.3

Promote Clinical Research on the Optimization of Existing Methods for Prevention, Diagnosis
and Treatment of Infectious Diseases ..................................................................................................... 67

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 2

Strategy 5.4

Promote Research and Development of Novel Methods for Prevention, Diagnosis and Treatment
and Promote the Cooperation of Industry, Academia and Government ................................................. 69

Strategy 5.5

Promote Global Research Collaboration on AMR and Research and Development of Novel
Methods for Prevention, Diagnosis and Treatment of Antimicrobial-Resistant Infections .................... 72

Strategy 5.6

Sustainable Research and Development of Antimicrobials and Enhancement of Stable Supply ........... 75

Goal 6 Enhance Global Multidisciplinary Countermeasures against Antimicrobial Resistance............................... 77
Strategy 6.1

Strengthen Japan’s Leadership for Global Policies on Antimicrobial Resistance .................................. 78

Strategy 6.2

Promote International Cooperation to Achieve the Global Action Plan on Antimicrobial
Resistance ............................................................................................................................................... 81

Outcome Indices for the Action Plan .............................................................................................................................. 84
Monitoring and Evaluation of Progress .......................................................................................................................... 87
Reference ........................................................................................................................................................................... 88

Glossary ......................................................................................................................................................... 88

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 3

INTRODUCTION
ANTIMICROBIAL RESISTANCE: A HEALTH THREAT
The term "Antimicrobial Resistance (AMR)" refers to the state in which certain types of antimicrobials such as
antibiotics and antivirals become less effective or ineffective. As the number of such bacteria and viruses with
antimicrobial resistance increases, conventional drugs become ineffective, making it difficult to treat infectious
diseases that were previously treatable with mild illnesses, and increasing the likelihood of serious illness and death.
Therefore, it is important to control the outbreak of antimicrobial resistance (AMR) wherever possible and preventthe spread of infectious diseases caused by antimicrobial-resistant organisms (AROs). Since the 1980s,
antimicrobial-resistant (AMR) bacteria that do not respond to conventional antibiotics have been identified aroundthe world, making it increasingly difficult to prevent and treat infections, and the number of infections that do notrespond to antibiotics is expected to continue to increase. In Japan, healthcare-associated infections caused byantimicrobial-resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) andvancomycin-resistant Enterococci (VRE), followed by multidrug-resistant Pseudomonas aeruginosa (MDRP) andmultidrug-resistant Acinetobacter (MDRA), have spread, and these infections are still major problems in healthcare
facilities. In addition, carbapenem-resistant Enterobacteriaceae (CRE), which are resistant to carbapenems, haveemerged recently.

Infections caused by antimicrobial-resistant organisms (AROs) are less easily recognized as a crisis than infections
that are considered more likely to cause rapid pandemics, such as the coronavirus infectious disease, emerged in2019 (COVID-19). Meanwhile, the review committee on antimicrobial resistance (AMR) in United Kingdom(O'Neill Commission) estimates that if no action is taken, the number of deaths worldwide will reach 10 million by
2050, exceeding the number of deaths from cancer. 1 In Japan, a 2019 survey reported that more than 8,000 annual
deaths in 2017 are estimated from bacteraemia2 caused by methicillin-resistant Staphylococcus aureus (MRSA) andfluoroquinolone-resistant E. coli (FQREC), which are the most frequently seen antimicrobial resistant bacteria inJapan.3

Furthermore, the economic impact of antimicrobial resistance (AMR) is also considered significant as in a 2017
World Bank study stating that if no action is taken, the world's annual Gross Domestic Product (GDP) could decline
by 3.8% by 2050 compared to 2017. Since this figure is comparable to the financial crisis that occurred in 2008, it
is also considered obvious that the world economy will be in a critical situation. 4

For all these reasons, antimicrobial resistance (AMR) has been taken up as a serious health threat worldwide andrecognized as one of the priorities for the Group of Seven (G7) to address in health sector, and the World HealthOrganization (WHO) has placed antimicrobial resistance (AMR) control on its important policy agenda. 5 As amember of the Group of Seven (G7), Japan is in a position to play a leading role in the combat against antimicrobial
resistance (AMR) not only domestically but also globally, especially in the Asian region.

1 Jim O'Neill, “The Review on Antimicrobial Resistance. Tackling Drug-Resistant Infections Globally: Final Report andRecommendations.,” May 2016
2 Bacteremia is a condition in which bacteria enter the bloodstream. Various infections can cause bacteremia, andbacteremia makes condition more severe and increases mortality rate.
3 S Tsuzuki, et al., National trend of blood-stream infection attributable deaths caused by Staphylococcus aureus andEscherichia coli in Japan. J Infect Chemother. 2020; 26(4): 367-371
4 World Bank, “Drug-resistant infections: a threat to our economic future: final report”, May 2017
5 World Health Organization, 10 global health issues to track in 2021, 24 December 2020

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 4

ACTION PLAN ON ANTIMICROBIAL RESISTANCE (AMR)
In order to suppress the occurrence of antimicrobial resistance (AMR) as much as possible and to prevent the spreadof infectious diseases caused by antimicrobial-resistant organisms (AROs), it is important to improve the knowledge
and understanding of the public, especially those engaged in the fields of health care, nursing and welfare, food,livestock and aquaculture, and agriculture, regarding antimicrobial resistance (AMR) and use of antimicrobials. In
addition, it is important to understand the occurrence of antimicrobial resistance (AMR) and the actual antimicrobialuse (surveillance, monitoring) and to assess risk based on these information; to work towards reducing antimicrobialresistant organisms (AROs) through appropriate infection prevention and control (IPC) and antimicrobial
stewardship (AMS); and to ensure effective means of prevention, diagnosis and treatment of antimicrobial resistantinfection (ARI), including research on mechanisms of the occurrence and spread of antimicrobial resistance (AMR)
and the socioeconomic impact, and research and development of new methods for prevention, diagnosis andtreatment.

The May 2015 World Health Assembly endorsed a global action plan on antimicrobial resistance (AMR), urging
member states to develop their own national action plans within two years. In order to promote and strengthen
domestic measures and international cooperation regarding antimicrobial resistance (AMR), the "Basic Guidelines
for Strengthening Measures on Emerging Infectious Diseases" was formulated at the "Ministerial Meeting on
Measures on Emerging Infectious Diseases" held on February 9, 2016, which includes description about theformulation of an action plan on antimicrobial resistance (AMR). Following this, at the "Ministerial Meeting on
Measures on Emerging Infectious Diseases" held on April 5, 2016, the "National Action Plan on Antimicrobial
Resistance (AMR) (2016-2020) " was formulated, which outlines measures to prevent the spread of infectious
diseases caused by antimicrobial-resistant organisms (AROs) while suppressing the occurrence of antimicrobial
resistance (AMR) as much as possible, with the aim of achieving a world without the disease burden caused byantimicrobial-resistant (AMR)-infectious diseases. The government has been making concerted efforts on
antimicrobial resistance (AMR).

Due to the spread of coronavirus infection disease, emerging in 2019 (COVID-19), the planning period of the"National Action Plan on Antimicrobial Resistance (AMR) (2016-2020)" has been extended to the end of FY2022,
and "National Action Plan on Antimicrobial Resistance (AMR) (2023-2027)" has been compiled to outline items to
be implemented over the next five years to further promote measures on antimicrobial resistance (AMR).

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 5

ABBREVIATIONSAMEDJapan Agency for Medical Research andDevelopment

DPC/PDPS

Diagnosis Procedure Combination / PerDiem Payment System

AMR

Antimicrobial Resistance

ESBL

Extended-spectrum beta-Lactamase

AMS

Antimicrobial Stewardship

EU

European Union

AMU

Antimicrobial Use

FAO

Food and Agricultural Organization of theUnited Nations

ARG

Antimicrobial-resistant Gene
FETP-J

Field Epidemiology Training Program Japan

ARI

Antimicrobial-resistant Infection
FQREC

Fluoroquinolone resistant Escherichia coli

ARISE

ARO Alliance for ASEAN & East Asia
G7Group of Seven

ARO

Antimicrobial-resistant Organism
GAIN Act

Generating Antibiotics Incentives Now Act

ASIARS-Net Asian Antimicrobial Resistance Surveillance
Network

GCP

Good Clinical Practice

ASP

Antimicrobial Stewardship Program

GDP

Gross Domestic Product

ASPIRE

Asia-Pacific One Health Initiative on AMR

GHIT Fund

Global Health Innovation Technology Fund

AST

Antimicrobial Stewardship Team

GHSA

Global Health Security Agenda

AUD

Antimicrobial Use Density

GLASS

Global Antimicrobial Resistance Surveillance
SystemCAUTI

Catheter-associated Urinary Tract Infection
GloPID-R

Global Research Collaboration for Infectious
Disease Preparedness

CCP

Critical Control Point

CDC

Centers for Disease Prevention and Control

HACCP

Hazard Analysis and Critical Control Point

CDI

Clostridium difficile Infection

HAI

Healthcare-associated Infection

CiCLE

Cyclic Innovation for Clinical Empowerment

Hib

Haemophilus influenzae type b

CLABSI

Central Line-associated Bloodstream Infection

ICD

Infection Control Doctor

CLSI

Clinical & Laboratory Standards Institute

ICH

COI

Conflict of Interest

International Conference on Harmonisation ofTechnical Requirements for Registration of
Pharmaceuticals for Human Use

COVID-19

Corona Virus Infectious Disease, emerged in 2019 ICMRA

CRE

Carbapenem- resistant Enterobacteriaceae

DALYs

Disability-adjusted life year

DDD

Defined Daily DoseDID

DDD per 1,000 inhabitants per day

DOTDays of Therapy

International Coalition of Medicines Regulatory
Authorities

ICT

Infection Control TeamICU

Intensive Care Unit

IDES

Infectious Disease Emergency Specialist(Training Program)

IHR

International Health Regulation

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 6

IPC

Infection Prevention and Control

OECD

Organisation for Economic Co-operation andDevelopment

JARBB

Japan Antimicrobial Resistant Bacterial Bank

JARBS

Japan Antimicrobial Resistant Bacterial
Surveillance

PCR

Polymerase Chain Reaction

PCU

Population-corrected Unit

JANIS

Japan Nosocomial Infections Surveillance

PK/PD

Pharmacokinetics/Pharmacodynamics

JICA

Japan International Cooperation Agency

POC

Point of CareJPIAMR

Joint Programming Initiative on Antimicrobial
Resistance

POT

PCR-based Open Reading Frame Typing

PPP

Public Private Partnership

PPS

Point Prevalence Survey

QALYs

Quality-adjusted life year

SMA

Sodium Mercaptoacetate

SNS

Social networking service

JSAC

Japan Surveillance of Antimicrobial Consumption

J-SIPHEJapan Surveillance for Infection Prevention and
Healthcare Epidemiology

JVARM

Japanese Veterinary Antimicrobial Resistance
Monitoring System

J-VEG

Japanese Veterinary Epidemiology and Genomics

SSI
MALDI-TOF MS Matrix-assisted Laser Desorption/Ionization TimeOf Flight Mass Spectrometry
TATFAR
MBL

Metallo-beta-lactamase

MEPM-R

Meropenem Resistance

MDRA

Multidrug-resistant Acinetobacter spp.

MDRP

Multidrug-resistant Pseudomonas aeruginosa

MRC

Medical Research Council

Surgical Site Infection
Transatlantic Task Force on Antimicrobial
Resistance

UNEP

United Nations Environment Programme

VICH

International Cooperation on Harmonisation ofTechnical Requirements for Registration of
Veterinary Medicinal Products

WGS

Whole Genome Sequencing

WHO

World Health Organization

WOAH

World Organisation for Animal Health

MRSA

Methicillin-resistant Staphylococcus aureus

NCGM

National Center for Global Health and Medicine
WPRO

Regional Office for the Western Pacific

NDB

National Database for Prescription and National
Health Check-up

VAP

Ventilator-associated Pneumonia

NICU

Neonatal Intensive Care Unit

VRE

Vancomycin-resistant Enterococci

NIH

National Institutes of Health

XDR

Extensively Drug-resistance

NOAR

Nippon AMR One Health Report

YLD

Years Lived with Disability

NTDs

Neglected Tropical Diseases

Note that in the following document, antimicrobial substances and drugs for human and animal use are collectively called"antimicrobials". Antimicrobials used specifically against bacteria are called "antibiotics". With regard to animals, only
antimicrobials against bacteria are discussed, of which "veterinary antibiotics" and "antibiotic feed additives" together are referred
to as "antibiotics for animals".

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 7

THE EFFORTS AND RESULTS OF THE NATIONALACTION PLAN ON ANTIMICROBIAL RESISTANCE(AMR) (2016-2020)
In order to promote measures against antimicrobial resistance (AMR), the National Action Plan on Antimicrobial
Resistance (AMR) (2016-2020) sets goals for a total of six areas: (1) Public Awareness and Education, (2)Surveillance and Monitoring, (3) Infection Prevention and Control, (4) Antimicrobial Stewardship, (5) Research andDevelopment, and (6) International Cooperation. The National Action Plan on Antimicrobial Resistance (AMR)(2016-2020) sets numerical targets as outcome indices throughout the entire process, and related ministries, agencies,
and organizations have worked together to intensively promote measures against antimicrobial resistance (AMR)
from the perspective of a global approach that transcends barriers between humans and animals (One Healthapproach).

PUBLIC AWARENESS AND EDUCATION
In order to promote the nationwide public awareness-raising activities on antimicrobial resistance (AMR), we havepromoted the establishment of the "Public Awareness Raising Meeting on Promoting Measures against
Antimicrobial Resistance (AMR)", the AMR Clinical Reference Center (AMRCRC), 6 which consolidates various
information on antimicrobial resistance (AMR) and provides information and training to medical professionals andlocal government officers, and the "Antibiotic Awareness Month". In addition, for professionals and workers invarious fields such as healthcare, nursing and welfare, food, veterinary medicine, livestock and aquaculture, andagriculture, we have been promoting education and training on antimicrobial resistance (AMR) through adding andenhancing items related to antimicrobial resistance (AMR) to curricula of educational programs for medical
professionals and other professionals.
On the other hand, the public’s awareness of antimicrobial resistance (AMR) is not at a high level, and the level ofunderstanding of the "National Action Plan on Antimicrobial Resistance (AMR)" in clinics nationwide is stillinsufficient. It is necessary to continue to conduct public awareness-raising activities using various methods.

SURVEILLANCE AND MONITORING
In order to strengthen the surveillance in the medical and nursing care fields, the establishment of a "Antimicrobial
Resistance Research Center" in the National Institute of Infectious Diseases, the operation of the "Japan Surveillance
for Prevention and Healthcare Epidemiology (J-SIPHE)" to consolidate information on healthcare-associatedinfections (HAIs), occurrence of antimicrobial-resistant bacteria, and antimicrobial use at participating facilities
nationwide, and the expansion of information collection on antimicrobial resistance rates in ambulatory and elderly
care facilities have been worked on.
In the field of livestock and aquaculture, the enhancement of the functions and systems of the National Veterinary
Assay Laboratory as a core laboratory, and the expansion of information collection on antimicrobial-resistantbacteria not only in livestock, but also in farm-raised aquatic animals and pets have been promoted.
In addition to these, from the viewpoint of promoting the One Health approach, the AMR Clinical Reference Center(AMRCRC) has been conducting nationwide surveillance and monitoring of antimicrobial resistance (AMR) by
disclosing and operating the Antimicrobial resistance (AMR) One Health Platform, which covers data not only inthe field of human medicine but also in a wide range of fields including veterinary medicine, animal and marine
medicine, agriculture, food hygiene and environment. In addition, the "Antimicrobial Resistance One-Health
Surveillance Committee" was established to study the status of the use of antimicrobials for humans and animals andthe antimicrobial resistance rates of microorganisms in Japan. The Group holds discussions among experts in thehuman, animal, and environmental fields, and annually produces a "Nippon AMR One Health Report (NOAR)" that
evaluates the current status and understanding of trends in each field.
6 An organization that consolidates information on antimicrobial resistance (AMR) in healthcare and welfare and provides

education and awareness for healthcare professionals, welfare workers, and public health-related local government officials.
It develops and produces educational materials, provides online information, and offers training opportunities. Establishedat the National Center for Global Health and Medicine.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 8

It is necessary to continue to promote understanding of antimicrobial resistance (AMR) trends that transcend theboundaries between humans, animals, and the environment, as well as to expand the number of target
microorganisms and participating facilities and strengthen the testing systems necessary for trend surveys in orderto implement antimicrobial resistance (AMR) countermeasures tailored to local needs.

INFECTION PREVENTION AND CONTROLWith regard to infection control measures at medical institutions, the revision of medical fee in FY2022 establishedthe premium for improvement of infection control measures from the viewpoint of promoting infection control
measures at individual medical institutions and infection control measures implemented in cooperation with local
medical institutions, while building on the premium for infection control measures. In addition, through the "Japan
Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE)," comparisons and evaluations
regarding infection prevention and control (IPC) have been conducted. On the other hand, current nosocomial
infection control measures mainly target medical institutions, and further promotion and strengthening of efforts inelderly care facilities are needed.
In the livestock and aquaculture field, we have supported the development and commercialization of vaccines,
immunostimulants, in vitro diagnostics, and reagents, and also made efforts to ensure compliance with the biosecurity
standards and to disseminate the guidebook for the biosecurity standards for each livestock species in order topromote production systems that do not rely on antimicrobials. Furthermore, in the food field, we have been
providing support to all food businesses that manufacture, process, prepare, and sell food, etc., so that they cansmoothly engage in Hazard Analysis and Critical Control Point (HACCP)7.

ANTIMICROBIAL STEWARDSHIPTo promote antimicrobial stewardship, the Ministry of Health, Labour and Welfare (MHLW) has formulated anddisseminated the Manual of Antimicrobial Stewardship. Also, in the revision of medical fee in FY2018, the premiumfor support for appropriate use of antibiotics and the premium for support for appropriate use of pediatric antibiotics
were established to support efforts to promote appropriate use of antimicrobials. In particular, the introduction of thepremium for support for appropriate use of pediatric antibiotics has resulted in a decrease of approximately 20% in
the administration of antibiotics to pediatric patients in outpatient clinics. 8 On the other hand, there are reports thatthe guidelines are not always followed in the use of broad antimicrobials in the medical field,9 10 and further efforts
are required to promote their appropriate use.
In the livestock and aquaculture field, guidelines for prudent use have been established to promote the thoroughimplementation of prudent use. In addition, the risk assessment concerning the impact of antimicrobial-resistantbacteria on human health through food has been completed for all antibiotic feed additives designated in Japan, andthe designation of five antibiotic feed additives11 that were assessed as potentially having adverse effects on humanhealth has been withdrawn. On the other hand, understanding of actual use of antimicrobials at production sites is an
issue, and a mechanism needs to be established.

7 Methods of food hygiene management that control particularly important processes that prevent foodborne bacterial

contamination and foreign material contamination that may occur from the time of arrival of raw materials to the time of
shipment.
8 Okubo Y, Nishi A, Michels KB, et al. The consequence of financial incentives for not prescribing antibiotics: a Japan's
nationwide quasi-experiment. Int J Epidemiol. 2022;51(5):1645-1655. doi:10.1093/ije/dyac057
9 Jung-ho Shin, Noriko Sasaki, Susumu Kunisawa, Yuichi Imanaka. Influence of criteria for nosocomial use of antimicrobial
agents on the selection of antimicrobial agents recommended in practice guidelines for patients with community-acquired
pneumonia, and the impact of its antimicrobial selection on outcomes. The 58th Annual Congress of Japan Society for
Healthcare Administration in Fukuoka and online, October 2-4, 2020 (Journal of the Japan Society for Healthcare
Administration Vol.57 Suppl. p.172)
10 2018 Ministry of Health, Labour and Welfare commissioned project: Evidence Based Medicine (EBM) Dissemination andPromotion Project “Medical Guideline Handbook” p3
11 Virginiamycin, colistin sulfate, tyrosin phosphate, chlortetracycline, alkyl trimethyl ammonium calcium oxytetracycline

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 9

RESEARCH AND DEVELOPMENT
With regard to research and development and drug discovery related to antimicrobial resistance (AMR) control
measures, in addition to the development of the Japan antimicrobial resistant bacterial bank (JARBB), the expansionof genome databases of human, animal, and environmental origin, and the promotion of clinical and epidemiologicalstudies on health economic evaluation and appropriate use of antimicrobials, Japan agency for medical research anddevelopment (AMED) has been promoting it through the "Research Project for the Promotion of Innovative Drug
Development for Emerging and Re-emerging Infections" and "Cyclic Innovation for Clinical Empowerment(CiCLE)" under an industry-academia-government collaboration system.
Although these efforts have produced some results, such as progress in research on antimicrobial resistance (AMR)
control measures, the development of new antibiotics in Japan has been stagnant since the 1990s. On the other hand,even if the number of drugs successfully developed and distributed in the market increases, inappropriate use of suchdrugs will lead to an increase in the number of antimicrobial-resistant bacteria and, consequently, a weakening of
their effectiveness, so it is necessary to control their use to an appropriate level. In the U.S., U.K., Sweden, market
incentives are being introduced on a trial basis to increase the predictability of post-marketing profits while
separating "usage (sales volume)" from "sales (profits)" (de-linking). In Japan, it is necessary to consider on a specificmethod to secure drugs for the treatment of antimicrobial resistant bacteria, such as market incentives. In addition,shortages of antibiotics are occurring all over the world, and Japan is also experiencing a large-scale shortage ofantibiotics. A stable supply of antibiotics is an important issue to promote their appropriate use and to control the
spread of antimicrobial resistance (AMR). In addition to promote research and development of new antibiotics,
measures to maintain a stable supply of antimicrobials are required.

INTERNATIONAL COOPERATION
Japan has supported the efforts of the World Health Organization (WHO), the Group of Seven (G7) process, theWorld Organisation for Animal Health (WOAH) and others by submitting data to the Global Antimicrobial
Resistance Surveillance System (GLASS) of the World Health Organization (WHO), holding the AMR One HealthTokyo Conference jointly with the Western Pacific Regional Office (WPRO), and providing data and advice for theestablishment of a database for the use of antibiotics for animals by the World Organisation for Animal Health(WOAH). In addition, Japan has been engaged in the discussion of the human field on the regulatory response
required to be implemented by regulatory authorities in the framework of the International Cooperation of Medicines
Regulatory Authorities (ICMRA), including Japan, the U.S., and the EU, and in the discussion of the animal fieldon the development of common global study guidelines in the framework of the International Cooperation on
Harmonization of Technical Requirements for Registration of Veterinary Medical Products (VICH). In addition, we
have been engaged in international cooperation, mainly in Asian countries, in the areas of infection prevention andcontrol (IPC), support for surveillance systems, development of a system infrastructure for collecting information on
antimicrobial-resistant bacteria, and transfer of antimicrobial resistant (AMR) testing technology. Antibiotic use inJapan has remained below the Organization for Economic Cooperation and Development (OECD) average, Japan
continues to play a leading role in the world, especially in the Asian region, in addressing antimicrobial resistance(AMR).

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 10

THE CURRENT STATE AND CHALLENGES
ANTIMICROBIAL RESISTANCE IN JAPANOFThe National Action Plan on Antimicrobial Resistance (AMR) (2016-2020) set numerical targets throughout theplan as performance indicators and has been working on antimicrobial resistance (AMR) measures to achieve thetargets.

Table 1 National Action Plan on Antimicrobial Resistance (AMR) (2016-2020) Outcome Indices

HUMAN-RELATED INDICES
1．Lower the penicillin resistance of Streptococcus pneumoniae to 15% or less in 2020
The penicillin resistance (hereinafter "resistance" refers to the proportion of isolates that are classified as"resistant" or "intermediate" in a standardized antimicrobial susceptibility test) of pneumococcus remains at
a higher level than in other developed countries. Since this index is lowering at an annual rate of approx.
2%, it is aimed to accelerate the lowering of the index at an annual rate of 5 to 6%, by promoting the
stewardship of oral cephalosporin and other antimicrobials, thereby achieving the resistance rate of the samelevel as in other developed countries in 2030.

2．Lower the methicillin resistance of Staphylococcus aureus to 20% or less in 2020
The methicillin (oxacillin) resistance of Staphylococcus aureus remains at a higher level than in otherdeveloped countries, and this index is lowering at an annual proportion of approx. 2%. The U.K. achieved
the annual lowering rate of 5% through the strengthened measures from 2006 to 2011. In Japan as well, by
ensuring infection prevention and control and promoting the stewardship of antimicrobials, it is aimed toaccelerate the lowering of the index at a rate of approx. 5%, thereby achieving the resistance rates of thesame level as in other developed countries.

3. Lower the fluoroquinolone resistance of Escherichia coli to 25% or less in 2020
The fluoroquinolone resistance of Escherichia coli is highly correlated to the use of fluoroquinolones andthe resistance is on the increase at an annual rate of 1.5%, which is a higher level than in other developed
countries. By promoting the stewardship of oral fluoroquinolones and other antimicrobials, it is aimed totake a downturn in this trend, and achieve the resistance rates of the same level as in other developed
countries.

4. Lower the carbapenem (imipenem) resistance of Pseudomonas aeruginosa to 10% or less in 2020
The carbapenem resistance of Pseudomonas aeruginosa stands at 20% as of 2014, which is not a high levelcompared to other countries. Since this index is lowering at an annual rate of 0.5%, it is aim to achieve theresistance rate of 10% or less, by accelerating the lowering rate to 1 to 2%.

5. Maintain the carbapenem resistance of Escherichia coli and Klebsiella pneumoniae at 0.2% or less in 2020
The carbapenem-resistant Enterobacteriaceae (CRE) infection globally expanding and forms a serious
health threat, due to the few treatment choices. Fortunately, the carbapenem-resistance of Escherichia coli
and Klebsiella pneumoniae remain low in Japan, respectively at 0.1% and 0.2% as of 2014. It is aimed tomaintain these resistance rates at the same level through adequate measures.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 11

6. Reduce the antimicrobial use per day per 1,000 inhabitants in 2020 to two-thirds of the level by 2013
7. Reduce the use of oral cephalosporins, quinolones, and macrolides per day per 1,000 inhabitants in 2020 by
50% from the level in 2013
8. Reduce the use of intravenous antimicrobials per day per 1,000 inhabitants in 2020 by 20% from the level in2013
The antimicrobial use per day per 1,000 inhabitants (antimicrobial use density) is estimated at 15.8 as of2013. This is a relatively small figure compared to Europe (see Figure 0.1). However, in the Netherlands,
where the antimicrobial use density is the smallest in Europe, the figure stands at 11.3, approximately twothirds the level in Japan. In the meantime, it is characteristic in Japan that the share of use of oral broadspectrum antibiotics is very high.

Among the oral antibiotics used in Japan in 2013, macrolides accounted for 33%, cephalosporins for 27%(of which third generation took up 80%), and quinolones for 19% (approx. 80% in total). By reducing theuse of these antibiotics by half, and reducing the use of intravenous antibiotics by 20% through thepromotion of antimicrobial stewardship, it is aimed to reduce the use of all oral antibiotics to two-thirds.

ANIMAL-RELATED INDICES
1．Lower the tetracycline resistance of Escherichia coli to 33% or less
The tetracycline resistance of Escherichia coli in livestock in Japan was lowered from 59.0% in 2001 to
45.2% in 2014 (Figure 0.4, Trends in antimicrobial resistance in Escherichia coli of farm animal origin in
Japan (2001-2014)). This was considered to have been achieved through measures for ensuring appropriate
antibiotic use. Therefore, it is deemed possible to accelerate the lowering of resistance rate by implementing
this action plan, and the target is set at 33% or less in 2020.
2．Maintain the third-generation cephalosporin resistance of Escherichia coli at the same level as in the other G7
countries as of 2020
3．Maintain the fluoroquinolone resistance of Escherichia coli at the same level as in the other G7 countries asof 2020
 In the "Ranking of the Importance of Antimicrobials against Bacteria which Affect Human Health throughFood Commodities", established by the Food Safety Commission (FSC), the third-generation cephalosporins
and fluoroquinolones are rated as critically important in human medicine. In Japan, the resistance rates ofEscharichia coli derived from cattle, swine and meat poultry to the third-generation cephalosporins andfluoroquinolones were mostly at the same levels as in the other G7 countries (Figure 0.3, International
comparison of antimicrobial resistance in Escherichia coli of farm animal origin (2013)). This was considered
to have been achieved through the specific risk management measures in Japan, including the requirement forprescription by veterinarians for the use of these antibiotics for animals, the use thereof only in cases whereother veterinary antibiotics are ineffective, and the mandatory post-marketing reporting periodicallyconcerning the emergence of resistant bacteria. While figures in Japan are already at the same level as in theother G7 countries at present, it is aimed to maintain them at the same level as in the other G7 countries as of2020 by implementing this action plan, because each G7 country is expected to implement their own action
plan to improve their levels in 2020.

Regarding the antimicrobial resistance rates in 2020, the carbapenem resistance rates of Escherichia coli and bacillus
pneumoniae has been increasing in recent years in many countries around the world, while in Japan the rate remains
at or below the 2013 level through the efforts based on the National Action Plan on Antimicrobial Resistance (AMR)(2016-2020). In addition, the carbapenem resistance rate of Pseudomonas aeruginosa is decreasing, and progress isbeing made, although numerical targets have not been achieved. On the other hand, fluoroquinolone resistance ratein
E. coli and methicillin resistance rate in Staphylococcus aureus continue to increase, with a slight decrease in 2021.
Penicillin non-susceptibility rates of Streptococcus pneumoniae in cerebrospinal fluid (CSF) specimens remain high.
Antibiotic use based on sales of human antibiotics was 9.77 DID in 2021, a decrease of 32.7% compared to 2013.
National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 12

Injectable antibiotics also decreased by 1.1% compared to 2013. Antibiotic use based on sales of oral antibiotics,
including oral cephalosporins, oral macrolides, and oral fluoroquinolones, decreased compared to 2013, but none of
the targets have been achieved, and continued efforts are needed.

Table 2 Human-related outcome indices of the National Action Plan: Isolation rate of specific antimicrobialresistant bacteria (%)＊12
2013

2014

2015

2016

2017

2018

2019

2020

2021

Streptococcus pneumoniae
penicillin
susceptibility rate, CSF specimens§

non- 47.4

47.0

40.5

36.4

29.1

38.3

32.0

33.3

59.5

Streptococcus

non- 3.2

2.5

2.7

2.1

2.1

2.2

2.2

3.5

3.4

pneumoniae

penicillin

2020 (Target)

15% or lesssusceptibility rate, other than CSF specimens§
Escherichia coli fluoroquinolone resistance rate

35.5

36.1

38.0

39.3

40.1

40.9

41.4

41.5

40.4

25% or less

Staphylococcus aureus methicillin resistance rate

51.1

49.1

48.5

47.7

47.7

47.5

47.7

47.5

46.0

20% or lessPseudomonas aeruginosa carbapenem resistance 17.1
rate (imipenem)
Pseudomonas aeruginosa carbapenem resistance 10.7

19.9

18.8

17.9

16.9

16.2

16.2

15.9

15.8

10% or less

14.4

13.1

12.3

11.4

10.9

10.6

10.5

10.3

10% or less

0.1

0.1

0.1

0.1

0.1

0.1

0.1

0.1

0.2

0.2

0.2

0.1

0.1

0.1

0.1

0.1

0.3

0.3

0.2

0.2

0.3

0.2

0.2

0.2

0.2% or less (samelevel) ¶0.2% or less (samelevel) ¶0.2% or less (same

0.6

0.6

0.5

0.4

0.5

0.4

0.4

0.4

rate (meropenem)
Escherichia coli carbapenem resistance rate 0.1(imipenem)
Escherichia coli carbapenem resistance rate 0.1(meropenem)
Klebsiella pneumoniae carbapenem resistance rate 0.3

level) ¶(imipenem)
Klebsiella pneumoniae carbapenem resistance rate 0.6

0.2% or less (same(meropenem)
level) ¶Reference: Nippon AMR One Health Report (NOAR) 2021
* Created based on Japan Nosocomial Infections Surveillance (JANIS) data. Data posted every two years starting in 2013 and every year since 2017.
§The 2014 Streptococcus pneumoniae penicillin non-susceptibility rate follows the Clinical & Laboratory Standards Institute (CLSI) 2007 criteria, withpenicillin MICs of 0.125 µg/ml or greater as resistant. However, in 2008, Clinical & Laboratory Standards Institute (CLSI) changed its criteria andseparated spinal fluid and non-spinal fluid specimens, and since 2015, Japan Nosocomial Infections Surveillance (JANIS) has also published separate
tabulations for spinal fluid and non-spinal fluid specimens.
¶Carbapenem resistance rates for E. coli and Klebsiella pneumoniae in 2014 were 0.1% and 0.2%, maintaining the same level of resistance rates in 2020.

Table 3 Human-related outcome indices of National Action Plan: Antibiotic use (DID) (sales volume basis)12
2013132021

Comparison to 2013

All antimicrobials

14.52

9.77

32.7% decrease

33% decrease

Oral cephalosporins

3.91

2.11

46.1% decrease

50% decrease

Oral fluoroquinolones

2.83

1.48

43.7% decrease

50% decrease

Oral macrolides

4.83

2.72

47.5% decrease

50% decrease

0.89

1.1% decrease

20% decrease

Intravenous antimicrobial
0.90
Reference: Nippon AMR One Health Report (NOAR) 2021
DID: Defined daily dose per 1,000 inhabitants per day

2020 (Target)

12 Nippon AMR One Health Report (NAOR) 2021
13 MurakiY, et al.“Japanese antimicrobial consumption surveillance: first report on oral and parenteral antimicrobial
consumption in Japan （2009–2013）” J Glob Antimicrob Resist. 2016 Aug 6;7:19-23.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 13

The inappropriate use of antimicrobials has been indicated as the background to the global spread of antimicrobial
resistance (AMR). According to Japan Surveillance of Antimicrobial Consumption (JSAC) report in 2020, total
antibiotic use in humans in Japan was approximately 10.8 per day per 1,000 inhabitants in 2020, which is low
compared to developed countries in the EU (Figure 1). However, oral cephalosporins, oral fluoroquinolones andmacrolides which were effective against a wide range of bacteria were frequently used in Japan, and penicillins wereless frequently used compared to other countries.
Figure 2 shows that the antimicrobial resistance rates in methicillin-resistant Staphylococcus aureus (MRSA) andthird-generation cephalosporin-resistant E. coli are higher in Japan than in other countries. The prevalence of
carbapenem-resistant Enterobacteriaceae (CRE), which is of particular concern around the world in recent years,
remains low with a percentage of 0.1-0.2% in Japan.

Figure 1. Comparison of antibiotic use for humans in EU countries and Japan14
GreeceRomania
Bulgaria
FranceSpain
Ireland
PolandItaly
Belgium
IcelandMalta
Luxembourg
UK
Croatia
Portugal
Slovakia
Denmark
Lithuania
NorwayFinland
LatviaHungary
Estonia
SwedenSlovenia
Austria
Netherlands
Japan

0

5

10

15

20

25

30

Defined Daily Doses/1,000 residents/day
Tetracyclines
Trimethoprim/sulfonamide combinations
cephalosporins and other β-lactams
Quinolones

Penicillins
Other microbials
Macrolides, lincosamides, and streptogramins

14

The AMR Clinical Reference Center (AMRCRC) Japan Surveillance of Antimicrobial Consumption (JSAC)
https://amrcrc.ncgm.go.jp/surveillance/010/ref/NDB_2013-2020_comparison_ecdc 20230119.pdf

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 14

Figure 2. International comparison of antimicrobial resistance rates in major microorganisms showing
tendency toward antimicrobial resistance in humans (2020)15
Staphylococcus
aureusmethicillin
resistance rate (%)

Netherlands
NorwayDenmark
SwedenFinland
Estonia
Luxembourg
Austria
Switzerland
IcelandGermany
UK
Belgium
LatviaCzech
Montenegro
Slovenia
Lithuania
Bulgaria
IrelandFrancePolandGeorgia
EU average
UkraineBosnia & Herzegovina
Malta
Hungary
Spain
RussiaSlovakia
Croatia
Portugal
TurkeyItaly
BelarusSerbiaGreeceNorth Macedonia
Romania
Japan
Cyprus
Kosovo

16.7%

48.1%
0%

20%

40%

60%

80%

NorwayNetherlands
Denmark
FinlandSwedenEstonia
FranceAustria
Switzerland
Belgium
Germany
Slovenia
UK
Iceland
Ireland
Luxembourg
Malta
Czech
Spain
Portugal
EU average
Lithuania
Croatia
PolandRomania
HungaryJapan
GreeceBosnia & Herzegovina
LatviaItaly
Slovakia
SerbiaCyprus
KosovoMontenegro
Bulgaria
Georgia
Belarus
RussiaUkraineTurkeyNorth Macedonia

E. colithird-generation
cephalosporin
resistance rate (%)

14.9%

21.0%

0%

20% 40% 60% 80% 100%

NorwayFinlandDenmark
IcelandNetherlands
SwedenEstonia
Switzerland
FranceUK
Germany
Austria
Slovenia
Belgium
Lithuania
Ireland
Bosnia & Herzegovina
KosovoCzech
Luxembourg
EU average
Portugal
Romania
LatviaSpain
Croatia
Hungary
GreecePolandSlovakia
Malta
SerbiaItaly
Montenegro
Japan
UkraineBulgaria
Georgia
Belarus
CyprusTurkeyRussiaNorth Macedonia

E. colifluoroquinolone
resistance rate(%)

23.8%

41.5%

0%

20%

40%

60%

80%

15 Methicillin resistance rate for Staphylococcus aureus, third-generation cephalosporin (cefotaxime) resistance rate for E.

coli, and fluoroquinolone (levofloxacin) resistance rate for E. coli are 2019 data submitted by countries to World HealthOrganization (WHO) Global Antimicrobial Resistance Surveillance System (GLASS). (The data in Japan are based on theJapan Nosocomial Infections Surveillance (JANIS) compiled by the World Health Organization (WHO) Global Antimicrobial
Resistance Surveillance System (GLASS) method, and are in column B of the linked spreadsheet.)(https://docs.google.com/spreadsheets/d/1Ej0a-av4V5uoFw19DfZoDvcLpdvHTscfXoqJgozGiwc/edit#gid=1592777314)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 15

Resistance rates to third-generation cephalosporins and fluoroquinolones in E. coli from healthy livestock animals
remained low. On the other hand, for tetracyclines, the antimicrobial resistance rate remained higher than the target
value even as sales volumes declined after 2018. It is necessary to continue to promote appropriate and prudent useof these antimicrobials and to monitor trends in their antimicrobial resistance rates.

Table 4 Animal- related outcome indices of National Action Plan: Isolation rate of specific antimicrobialresistant bacteria (%)16
2014

2015

2016

2017

2018

2019

2020

E. coli tetracycline resistance rate (Farm)
45.2(Slaughterhouse)
E. coli third generation cephalosporin resistance rate 1.5(Farm)(Slaughterhouse)
E. coli fluoroquinolone resistance rate (Farm)
4.7(Slaughterhouse)
Reference: Nippon AMR One Health Report (NOAR) 2021

39.9
39.8
0.9

47.6

40.8

43.6

44.3

45.0

0.7
3.8
2.7

2020 (Target)
33% or lessSame level as Group of Seven(G7) countries17, 18

2.4

2.1

1.1

2.1

1.4

5.0

4.0

4.7

5.1

5.2

Same level as Group of Seven(G7) countries

The current state of antimicrobial resistance (AMR) in livestock in different countries is not simply comparable
because of the differences in target animals and survey methods. Concerning Escherichia coli, an indicator bacterium
for monitoring antimicrobial resistance (AMR), the prevalence of antimicrobial resistance (AMR) (Figure 3) in theGroup of Seven (G7) countries shows that the percentages of isolates resistant to tetracyclines, third-generation
cephalosporins, and fluoroquinolones in Japan are at comparable levels to those in Western countries. The resistance
rates of Tetracyclines, which are largely used in livestock, and the third-generation cephalosporins andfluoroquinolones, which are ranked by the Food Safety Commission of Japan (FSC) as critically important in humanhealthcare, in the Ranking of the Importance of Antimicrobials against Bacteria which Affect Human Health throughFood Commodities, were similar to those in Western countries.

As for the current status of antimicrobial use in the livestock field, a simple international comparison cannot be madebecause each country’s number of livestock, weight of livestock, surveyed agents, and survey methods are different,
but looking at the amount of antimicrobials used in livestock in the Group of Seven (G7) countries (Figure 4), theUnited States has the highest use, while Japan is at the same level as Germany and Italy.

16 Compiled

and partly modified from "Monitoring of AMR" by the National Veterinary Assay Laboratory, Ministry ofAgriculture, Forestry and Fisheries. JVARM, "Results of Antimicrobial Resistance Monitoring of Livestock-Derived Bacteria
on Farms" https://www.maff.go.jp/nval/yakuzai/yakuzai_p3.html
17
NARMS:
https://www.fda.gov/animal-veterinary/national-antimicrobial-resistance-monitoring-system/narms-nowintegrated-data
18 EFSA: https://www.efsa.europa.eu/en

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 16

Figure 3. International comparison of antimicrobial resistance rates in Escherichia coli of livestock origin(2020)19
USA

USA

USA
The resistant rate
to third-generation
cephalosporin (%)

The resistat rate
to tetracycline (%)
CanadaCanadaGermany

Germany

Pig
UK

Broiler

CanadaGermany
CattleCattleCattleFranceFranceFrancePig
Broiler

UK

Italy

Italy

Japan

Japan

Japan

40

80

(%)

0

40

80

Pig
Broiler

UK

Italy

0

The resistant rate
to fluoroquinolone (%)

0

(%)

40

80

(%)

Data for the U.S. is at 2019, data for Canada is at 2018, and the data for cattle and swine for Germany, France, the U.K. and Italy is at 2019.

Figure 4. International comparison of antibiotic use in the animal field (2020) 20
(ｔ)
6000
5000
4000
3000
2000
1000
0

USA

CanadaGermany

France

UK

Italy

Japan

19 Ministry of Agriculture, Forestry and Fisheries National Veterinary Assay Laboratory "Monitoring of AMR" The European

Union Summary Reporton Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2019–2020, Canadian
Integrated Program for Antimicrobial Resistance Surveillance(CIPARS)2018, National Antimicrobial Resistance Monitoring
System for Enteric Bacteria (NARMS)
20 U.S.: Summary Report On Antimicrobials Sold or Distributed for Use in Food-Producing Animals (fda.gov); Canada:
Canadian Antimicrobial Resistance Surveillance System Report; U.K., Italy, Germany and France: Sales of veterinary
antimicrobial agents in 31 European countries in 2016-2020; Japan: Annual Report of Sales Amount and Sales Volume of
Veterinary drugs
Note that some of the data in the U.S., Canada, EU, and Japan include data of pets and horses, etc. Data in each country
show the total amount of antimicrobials used for the total number of livestock in each country.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 17

NATIONAL ACTION PLAN ON ANTIMICROBIALRESISTANCE (AMR) (2023-2027)
To date, based on the National Action Plan on Antimicrobial Resistance (AMR) (2016-2020), relevant ministries,
agencies, and organizations have been working closely together to achieve a world free from the disease burdencaused by infectious diseases due to antimicrobial resistance (AMR), taking measures to reduce the occurrence ofantimicrobial resistance (AMR) as much as possible and to prevent the spread of infectious diseases caused byantimicrobial-resistant organisms (AROs). Some of the outcome indicators have shown improvements in responseto these efforts, however, there are indicators that have shown little improvements and newly emerging issues.
Continued efforts to combat antimicrobial resistance (AMR) in coordination with international movements areneeded.
In order to promote seamless antimicrobial resistance (AMR) control measures, it is important to continue to set
goals related to the following six areas: (1) Public awareness and education, (2) Surveillance and monitoring, (3)Infection prevention and control, (4) Antimicrobial stewardship, (5) Research and development, and (6) International
cooperation, and promote antimicrobial resistance (AMR) control measures toward achieving these goals.
Furthermore, at the 2021 Group of Seven (G7) Climate and Environment Ministers' meeting, for the first time,
antimicrobial resistance (AMR) was included in the meeting communiqué, and at the 2021 Group of Seven (G7)
Carbis Bay Leaders' Communiqué, the Health Declaration was endorsed that agreed to strengthen an One Healthapproach. By appropriately responding to the global promotion of the One Health approach and continuing its
advanced efforts, Japan can play a leading role in international actions, thereby contributing to protecting the healthand lives of its citizens and leading the world in the combat against antimicrobial resistance (AMR).
Therefore, "National Action Plan on Antimicrobial Resistance (AMR) (2023-2027)" has been established to further
promote antimicrobial resistance (AMR) control measures.
The National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) sets goals (major items) in the six areas
and, in each area, establishes strategies (medium items) to achieve the goals and specific actions (minor items) toimplement the strategies. For the strategies to achieve the goals, the objectives, background, specific action items,
relevant government agencies and organizations, and evaluation indices for each strategy should be described (Figure5). In addition, numerical targets throughout the National Action Plan are set as outcome indices.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 18

Figure 5. The Framework of the National Action Plan on antimicrobial resistance (AMR) and the Descriptionof Each Strategy

Action Plan

Description of Each Strategy
Objective

Background
Policies
Actions

Strategy
ActionRelated Ministries, Agencies, andInstitutions
Evaluation Indices

ActionStrategy

Outcome Indices of the National Action Plan

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 19

Table 5 Goals and Strategies in Six Areas of Countermeasures on Antimicrobial Resistance (AMR)
Goal 1
Public Awareness andImprove Public Awareness and Understanding, and Promote Education and Training of Professionals

Education
Strategy 1.1

Promote Public Awareness-raising Activities to Improve Public Knowledge and Understanding of AMR

Strategy1.2

Promote Education and Training on AMR of Professionals Involved in Related Fields

Goal 2
SurveillanceandMonitoring

Continuously Monitor Antimicrobial Resistance and Use of Antimicrobials, and Appropriately
Understand the Signs of Change and Spread of Antimicrobial Resistance

Strategy 2.1

Strengthen the Surveillance of Antimicrobial Resistance in Healthcare and Nursing Care

Strategy 2.2

Monitor the Trend of the Antimicrobial Use at Medical Institutions

Strategy 2.3

Strategy 2.4
Strategy 2.5
Goal 3
Infection

Prevention

and Control
Strategy 3.1

Strategy 3.2
Strategy 3.3

Strengthen Antimicrobial Resistance Surveillance in the Fields of Veterinary Medicine, Livestock andAquaculture, and others
Standardize Methods of Laboratory Testing and Strengthen Testing Functions of Antimicrobial
Resistance at Clinical, Commercial and Public Health Laboratories
Implement Integrated One Health Surveillance Including Humans, Animals, Food, and the Environment
Prevent the Spread of Antimicrobial-resistant Organisms by Implementing Appropriate Infection
Prevention and Control
Infection Prevention and Control in Healthcare and Nursing Care and Promotion of Regional
Cooperation
Promote Infection Prevention and Control in Livestock and Aquaculture, Veterinary Medicine and Food
Chain
Strengthen the Outbreak Response Capacity against Antimicrobial-resistant Infections

Goal 4
Antimicrobial

Promote Appropriate Use of Antimicrobials in the Fields of Healthcare, Livestock and Aquaculture

Stewardship
Strategy 4.1
Strategy 4.2
Goal 5
ResearchandDevelopment
Strategy 5.1

Strategy 5.2

Strategy 5.3

Strategy 5.4
Strategy 5.5

Promote Antimicrobial Stewardship at Medical Institutions
Ensure Prudent Use of Antibiotics for Animals in the Field of Livestock and Aquaculture and Veterinary
Medicine
Promote Research on Antimicrobial Resistance and Foster Research and Development to Secure theMeans to Prevent, Diagnose and Treat the Antimicrobial-resistant Infections
Promote Research to Elucidate the Mechanism of the Emergence and Transmission of Antimicrobial
Resistance and its Socioeconomic Impact
Promote Research on Public Awareness/Education on Antimicrobial Resistance, Infection Prevention
and Control, and Antimicrobial Stewardship
Promote Clinical Research on the Optimization of Existing Methods for Prevention, Diagnosis andTreatment of Infectious Diseases
Promote Research and Development of Novel Methods for Prevention, Diagnosis and Treatment andPromote the Cooperation of Industry, Academia and Government
Promote Global Research Collaboration on Antimicrobial Resistance and Research and Development of

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 20

Novel Methods for Prevention, Diagnosis and Treatment of Antimicrobial-resistant Infections
Strategy 5.6

Sustainable Research and Development of Antimicrobials and Enhancement of Stable Supply

Goal 6
International

Enhance Global Multidisciplinary Countermeasures against Antimicrobial Resistance

Cooperation
Strategy 6.1

Strengthen Japan’s Leadership for Global Policies on Antimicrobial Resistance

Strategy 6.2

Promote International Cooperation to Achieve the Global Action Plan on Antimicrobial Resistance

Table 6 National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) Outcome Indices

HUMAN-RELATED INDICES
1. Maintain the number of patients with vancomycin-resistant Enterococci (VRE) infections in 2027 at 80 or less(the level as of 2019)2.

Lower the methicillin resistance of Staphylococcus aureus to 20% or less by 2027

3.

Maintain the fluoroquinolone resistance of E. coli at 30% or less in 2027

4.

Lower the carbapenem (MEPM=R) resistance of Pseudomonas aeruginosa to 3% or less by 2027

5.

Maintain a carbapenem resistance of E. coli and Klebsiella pneumoniae at 0.2% or less in 2027

6.

Reduce antimicrobial use per day per 1,000 inhabitants by 15% from 2020 levels by 2027

7. Reduce the use of oral third generation cephalosporins, oral fluoroquinolones, and oral macrolides per day per
1,000 inhabitants by 40%, 30%, and 25%, respectively, from 2020 levels by 2027
8.

Reduce the use of intravenous carbapenems per day per 1,000 inhabitants by 20% from 2020 levels by 2027

ANIMAL-RELATED INDICES
1. Lower the tetracycline resistance of E. coli to 20% or less in cattle, 50% or less in swine, and 45% or less inchickens by 2027.
2. Lower the third-generation cephalosporin resistance of E. coli to 1% or less in cattle, 1% or less in swine, and
5% or less in chickens by 2027.
3. Lower the fluoroquinolone resistance of E. coli to 1% or less in cattle, 2% or less in swine, and 15% or less inchickens by 2027.
4.

Reduce the total use of veterinary antibiotics in the livestock field by 15% from 2020 levels by 2027.

5. Reduce total use of second-line drugs (third-generation cephalosporins, 15-membered macrolides(tulathromycin and gamithromycin), fluoroquinolones, and colistin) in the livestock field to 27 t or less in 2027.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 21

GOAL 1
IMPROVE PUBLIC AWARENESS AND
UNDERSTANDING, AND PROMOTE EDUCATION
AND TRAINING OF PROFESSIONALS

Strategies(1.1)

Promote Public Awareness-raising Activities to Improve
Public Knowledge and Understanding of AMR(1.2)

Promote Education and Training on AMR of Professionals
Involved in Related Fields

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 22

STRATEGY 1.1

PROMOTE PUBLIC AWARENESS-RAISING
ACTIVITIES TO IMPROVE PUBLIC KNOWLEDGE
AND UNDERSTANDING OF AMRBACKGROUND

Promotion of nation-wide measures against antimicrobial resistance (AMR) requires public awareness andunderstanding of antimicrobial resistance (AMR) and antimicrobials. Since the formulation of the "National
Action Plan on Antimicrobial Resistance (AMR) (2016-2020) ", various educational materials and tools havebeen distributed in various regions, information has been disseminated through websites and media, andeducational awareness-raising activities have been held for the public through some awareness-raising events.

Junior high school and senior high school students learn about infectious disease control and the importance ofusing medicines appropriately, as part of their health education at schools.21

However, in an awareness survey conducted in Japan in 2020, only 40% to 50% of all respondents had heardof the term "antimicrobial resistance", indicating that the awareness of antimicrobial resistance (AMR) is not
at a high level.22 23 In addition, in an awareness survey conducted in Japan in 2022, only 16.4% of respondents
correctly answered that "the statement 'Antibiotics knock out viruses' is wrong" and only 28.3% correctly
answered that "the statement 'Antibiotics should be stopped as soon as the patient is cured' is wrong".24In the above awareness survey, 27.4% of respondents indicated that they have antibiotics kept at home, and25.5% of respondents indicated that they have taken the antibiotics they kept at their own discretion, indicatingthat there are a certain number of people who take antimicrobials using their own judgment. Furthermore, inthe 2020 awareness survey, 34.6% of respondents said they did not finish their medication correctly when they
were prescribed with antibiotics. 25 Such inappropriate use of antimicrobials in amounts and duration can
encourage the emergence of antimicrobial resistance (AMR).



Therefore, it is important to promote public awareness and education regarding knowledge and understandingof antimicrobial resistance (AMR). In particular, targeted outreach for specific audience, including young
children and their guardians, and elderly people, to whom antimicrobials are often prescribed, will continue tobe important. 26 Moreover, it is important to acknowledge people, not discriminating against patients with
antimicrobial-resistant infections (ARI) in awareness-raising activities.

POLICIESCreate tools which aid proper awareness and understanding of antimicrobial stewardship (AMS), infection
prevention and control (IPC), and global efforts that transcend the boundaries between humans and animals(One Health approach), for the purpose of raising the public awareness of antimicrobial resistance (AMR). 

Develop a national campaign against the threat of antimicrobial resistance (AMR) in cooperation with relevant
agencies, organizations, and media organizations throughout the year and ensure that appropriate drugs are used
when necessary and in appropriate quantities and for appropriate durations for the purpose of increasing
nationwide public awareness and understanding of antimicrobial resistance (AMR).



Implement targeted awareness raising activities for specific audience, including young children and theirguardians, and elderly people, to whom antimicrobials are often prescribed, as well as companies with business
related to antimicrobial resistance (AMR) and academic groups in healthcare, animal health, and food hygiene.

21 Ministry of Education, Culture, Sports, Science and Technology “For the Healthy Life” (Senior High School Edition, 2020)
22 Cabinet Office, Public Opinion Poll on Infectious Diseases for which Drugs Do Not Work (Antimicrobial resistance),

August, 201923 Health and Labor Sciences Research Ohmagari Group, Health, Welfare and Labor Administration Promotion Survey
Project Fund Research, Research on the Implementation of National Action Plan on Antimicrobial Resistance (AMR), May
2020
24 Antibiotic Awareness Survey Report 2022 (Online survey, August, 2022), National Center for Global Health and Medicine
AMR Clinical Reference Center（https://amr.ncgm.go.jp/pdf/20220930_report_press.pdf）
25 Antibiotic Awareness Survey Report 2020 (Online survey, August, 2020), National Center for Global Health and Medicine
AMR Clinical Reference Center（https://amr.ncgm.go.jp/pdf/20201006_report.pdf）
26 Plan national d’alerte sur les antibiotiques 2011-2016, Ministère du Travail, de L’emploi et de la Santé, France, 2011

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 23

Key Messages to Raise Public AwarenessState of Antimicrobial Resistance: Seriousness of the problem, the world situation, the reality in Japanand its position in the world.



Antimicrobial Stewardship: Antibiotics are not effective for most cases of the common cold, andunnecessary use of antimicrobials breeds the emergence of antimicrobial-resistant organisms (AROs).

Infection Prevention and Control: Practicing the etiquette of covering coughs, handwashing, andreceiving vaccination (Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and influenza)
are key to prevent infections.



One Health approach: Integrated efforts across the areas, including human healthcare, veterinary
medicine, livestock and aquaculture, food hygiene, and environment, are important to combat
antimicrobial resistance (AMR).

ACTIONSFor General Population
Conduct government-wide conferences and other activities related to awareness-raising

Develop and provide awareness-raising toolsRun a platform (website) to communicate information on antimicrobial resistance (AMR) and disseminate
information through social networking services (SNS) and media

Implement awareness-raising events in collaboration with the Antibiotic Awareness Month

Make thorough risk communication 27 in the areas of human, veterinary medicine, livestock andaquaculture, and food hygieneImplement regular surveys on the knowledge, attitude, and practice regarding antimicrobial resistance(AMR)

For Specific Populations
Scope: Inpatients and outpatients, young children and their guardians, elderly people, and care facility residents

Develop and provide awareness-raising tools tailored to the nature and needs of each audience

Scope: Junior high school and high school students
Promote education regarding infectious disease control and the importance of using medicine appropriately

Scope: Travelers to overseas destinations
Provide information regarding antimicrobial resistance (AMR) through websites for travelers to overseas
destinations28

27 In the entire process of risk analysis, stakeholders such as the general public (consumers, consumer organizations),

government (risk management organizations, risk assessment organizations), media, businesses (primary producers,
manufacturers, distributors, industry associations, etc.), and experts (researchers, research and educational institutions,medical institutions, etc.) exchange information and opinions about risks and risk factors from their respective perspectives
mutually. Risk communication can deepen the knowledge of the characteristics of the risks to be considered and theireffects, and in the process deepen mutual understanding among the parties involved, building trust and allowing risk
management and risk assessment to function effectively. The purpose of risk communication is an activity of "dialogue, coconsideration, and collaboration" (engagement), not persuasion. This is based on the idea that the public should be involved
as stakeholders in decisions.
28 The examples are: Overseas Safety HP, Ministry of Foreign Affairs (MOFA) (http://www.anzen.mofa.go.jp), Ministry of
Health, Labour and Welfare (MHLW) website (http://www.mhlw.go.jp), For Traveler’s Health (FORTH), Ministry of Health,Labour and Welfare (MHLW) (http://www.forth.go.jp)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 24

Scope: Companies with business related to antimicrobial resistance (AMR) or antimicrobials and academic
groups in healthcare, animal health, and food hygiene

Develop guidance for non-public sectors to implement their own awareness-raising activities (withconsideration of conflict of interest (COI))

Request a statement of cooperation for countermeasures against antimicrobial resistance (AMR)

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONS
Office for COVID-19 and Other Emerging Infectious Disease Control, Cabinet Secretariat (CAS); Food Safety
Commission of Japan (FSC), Cabinet Office (CAO); Ministry of Foreign Affairs (MOFA); Ministry of Education,
Culture, Sports, Science and Technology (MEXT); Ministry of Health, Labour and Welfare (MHLW); Ministryof Agriculture, Forestry and Fisheries (MAFF); Ministry of the Environment (MOE)EVALUATION INDICESLevel of antimicrobial resistance (AMR) awareness and comprehension



Number of antimicrobial resistance (AMR) awareness-raising tools distributed

Number of accesses to the antimicrobial resistance (AMR) information platform (website) and social
networking services (SNS)National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 25

STRATEGY 1.2

PROMOTE EDUCATION AND TRAINING ON AMR
OF PROFESSIONALS INVOLVED IN RELATEDFIELDSBACKGROUNDReducing the emergence and spread of antimicrobial resistance (AMR) requires antimicrobial stewardship(AMS) and infection prevention and control (IPC). To foster antimicrobial stewardship (AMS) and infection
prevention and control (IPC) among professionals dealing with antimicrobials and infectious diseases, their
behavioural change based on increased knowledge and understanding of antimicrobial resistance (AMR) is
critical in addition to the strengthening regulations.



Educational interventions for health care workers have had some impact. For example, a workshop-based
intervention for community general practices in the United Kingdom was shown to reduce antimicrobial
prescribing by 6.1% in these practices.29 Another study found that online training of general practitioners in
the Netherlands resulted in a 21% antimicrobial prescription rate in the intervention group, compared to a 33%
rate in the control group.30

Japan, however, has only a small number of experts of infectious disease control. For example, there are 1,554
physicians specialized in infectious disease, which are approximately 1/15th of board-certified surgeons and1/3rd of acute care surgeons, as of July 2022. Moreover, there are 531 physicians working in infectious diseasedepartments, which is only 0.2% of total working physicians in hospitals and clinics. 31 Number of othercertified healthcare professions in infectious disease control is significantly limited; there are 3,312 Certified
Nurses in Infection Control, 100 Certified Nurse Specialists in Infection Control Nursing, 1,045 Certified
Pharmacists in Infection Control, and 776 Infection Control Microbiological Technologists, as of December
2021.32In addition, according to an awareness survey conducted among clinics nationwide in 2020, only 31.3% of
respondents said they "can explain/understand the "National Action Plan on Antimicrobial Resistance (AMR)"
to others," 54.4% said that "antimicrobial stewardship has a great effect in reducing antimicrobial resistance,"and only 71.1% of the respondents said that they "rarely prescribe antibiotics when diagnosing a common cold
(0-20%)".33The roles of veterinarians and those engaged in livestock and aquaculture industry who use veterinary
antibiotics or antibiotic feed additives are especially significant in reducing risk in the field of livestock andaquaculture. They need to use antibiotics with correct understanding of antimicrobial resistance (AMR) andappropriate and prudent use of antibiotics.

These efforts to promote and educate those who use these antimicrobials and those involved in infection
prevention and control (IPC) of microorganisms regarding antimicrobial resistance (AMR) need to be further
enhanced.

29 McNulty C, Hawking M, Lecky D, et al. Effects of primary care antimicrobial stewardship outreach on antibiotic use by

general practice staff: pragmatic randomized controlled trial of the TARGET antibiotics workshop. J Antimicrob Chemother.
2018;73(5):1423-1432. doi:10.1093/jac/dky004
30 Dekker ARJ, Verheij TJM, Broekhuizen BDL, et al. Effectiveness of general practitioner online training and an information
booklet for parents on antibiotic prescribing for children with respiratory tract infection in primary care: a cluster randomized
controlled trial. J Antimicrob Chemother. 2018;73(5):1416-1422. doi:10.1093/jac/dkx542
31
List
of
physicians
specializedininfectious
disease
(July
1,
2022)
（https://www.kansensho.or.jp/uploads/files/senmoni/meibo_220701.pdf）
32 Japanese Nursing Association Credentialing system (http://nintei.nurse.or.jp/nursing/qualification/), Certified nurse
specialists in infection control nursing (http://www.ncn.ac.jp/examination/grad/050/026advanced.html), Certified Pharmacist
in Infection Control (https://www.jshp.or.jp/snmon/senmon2.html), Infection Control Microbiological Technologist (ICMT)
system (http://www.jscm.org/icmt_new/index.html)
33 Gu, et al., The Japanese Association for Infectious Diseases Joint Commission of Inquiry for Outpatients Antimicrobial
Use, The 2nd Nationwide Questionnaire Survey on Antimicrobial Stewardship with Clinic Physicians, Japanese Journal of
Chemotherapy 69(Suppl.A)195, April 2021

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 26

POLICIES

Accumulate the necessary knowledge, enrich practical education programs, and promote their use in relevantorganizations in order to improve knowledge on antimicrobial resistance (AMR), and promote education on
infection prevention and control (IPC) and antimicrobial stewardship (AMS) among professionals and workers
in various areas, including healthcare, nursing care, food, veterinary medicine, livestock and aquaculture, andagricultureEnhance and promote a continuous antimicrobial resistance (AMR) educational system covering undergraduate
education and post-graduate training

Put in place a system for shared access to infectious disease experts in regions, and create a platform for relevant
professionals to easily access information

ACTIONS

Undergraduate/Graduate Education
Scope: Undergraduate/Graduate students pursuing careers in human healthcare 34 , veterinary medicine 35 ,nursing care and public welfare36, agriculture, livestock and aquaculture and food hygieneContinue to promote the educational activities in related institutions as the contents related to antimicrobial
resistance (AMR), infection prevention and control (IPC), and antimicrobial stewardship (AMS) in thebasic education for various professions

National Qualification
Scope: Examinees to be qualified as professionals in healthcare, veterinary medicine, nursing care, and publicwelfare

Establish and continue the subjects on antimicrobial resistance (AMR), infection prevention and control(IPC), and antimicrobial stewardship (AMS) in standard questions for qualifying examinations, as
appropriate

Post-Graduate Education and Training
Scope: Physicians and dentists


Implement antimicrobial stewardship (AMS) education in residency systems for physicians and dentists,
as appropriate (see Strategy 4.1)

Scope: Pharmacists

Develop and introduce standard training programs on antimicrobial resistance (AMR), infection
prevention and control (IPC), and antimicrobial stewardship (AMS) in clinical training

Scope: Veterinarians

Implement training programs related to antimicrobial resistance (AMR) in post-graduate clinical trainingImprove and implement seminars and training for livestock health inspectors and clinical veterinarians

Scope: Healthcare professionals other than physicians, dentists, and pharmacists, and other workers in medical
institutions37
Develop and improve training programs related to infection prevention and control (IPC) in post-graduate
introductory training

34 Physicians, dentists, pharmacists, registered nurses, licensed practical nurses, midwives, public health nurses, medical

technologists, radiological technologists, clinical engineering technologists, speech-language-hearing therapists, physicaltherapists, occupational therapists, dental hygienists, registered dietitians, etc.
35 Veterinarians, veterinary nurses for companion animals, etc.
36 Social workers, certified care workers, psychiatric social workers, care managers, home care workers, etc.
37 Those who work in medical institutions and may directly contact patients or patients’ biological fluids, including nursing
assistants, health fitness programmers, health information managers, medical assistants, physician administrative assistant,clinical research coordinator, linen keepers, janitors, and guards

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 27Continuing Education
Scope: Healthcare professionals, other workers in medical institutions, professionals in veterinary medicine,and professionals in livestock and aquaculture, and agricultureContinue and improve training programs related to infection prevention and control (IPC) (such as theimportance of hand hygiene) and antimicrobial stewardship (AMS) in continuing education

Promote appropriate administration of antibiotics by disseminating educational programs utilizing theantimicrobial susceptibility table (antibiogram) for healthcare professionals



Encourage relevant groups including academic societies to use the training programs and enhance relevant
trainingSupport education and training through the infectious disease education professional network (Infectious
Disease Education Consortium)38

Implement seminars and training for livestock producers, aquaculture farmers, and feed manufacturers,
and ensure prefectures to instruct on-site practices in veterinary medicine and livestock production, and toraise thorough awareness thereon

Scope: Responsible local government officers

Continue and improve training programs related to outbreaks of antimicrobial-resistant infections (ARIs)
as a part of professional education and training (see Strategy 3.3)

Promote use of the training programs and enhancement of relevant trainingEnhance relevant seminars and training (see Strategy 3.3)

Professional Education
Scope: Qualified professionals39 and examinees for qualification by health care groups, academic associations,and certification authorities regarding infectious diseases


Encourage relevant groups to include antimicrobial resistance (AMR)-related training in the requirementsfor qualification and renewing of qualification

Enhance training systems for field epidemiology within hospitals (hospital epidemiology) (see Strategy
2.1and Strategy 3.3)

Scope: Physicians, dentists, pharmacists, medical technologists, and nurses other than those described aboveProvide support to promote antimicrobial resistance (AMR)-related requirements to be included in existing
relevant qualifications

Scope: Veterinarians
Consider instituting a certification system for the appropriate management of infectious diseases inveterinary medicine

38 A network across disciplines (medical, animal, food, infection prevention and control, appropriate use of antimicrobials,etc.) that brings together human resources capable of providing education on infectious diseases. Since the number of
personnel who can provide education and training on antimicrobial resistance (AMR) is limited, the network will develop
educational tools and train personnel for education and training activities
39 Qualifications related to infection prevention and control: Infection Control Doctor (Japanese College of Infection Control
Doctors), Certified Nurse Specialist in Infection Control Nursing and Certified Nurse in Infection Control (Japanese Nursing
Association), Board Certified Infection Control Pharmacy Specialist and Board Certified Pharmacist in Infection Control(Japanese Society of Hospital Pharmacists), Infection Control Microbiological Technologist (Japanese Society for ClinicalMicrobiology), Board Certified Physician and Dental Hygienist in Nosocomial Infection Prevention and Control (Japanese
Association for Oral Infectious Diseases), Certified Sterilisation Specialist (Japanese Society of Medical Instrumentation),and other private qualifications
Qualifications by academic associations related to infectious disease consultation: Certified Infectious Disease Specialist(The Japanese Association for Infectious Diseases), Japanese Antimicrobial Chemotherapy Physician (JACP), Fellow of
JACP (Japanese Society of Chemotherapy), Japanese Antimicrobial Chemotherapy Dentist (JACD), Fellow of JACD
(Japanese Society of Chemotherapy), and Japanese Antimicrobial Chemotherapy Pharmacist (Japanese Society of
Chemotherapy)
Outpatient Anti-infective Agent Pharmacist (Japanese Society of Chemotherapy), Board certified Pharmacotherapy
Specialist (The Japanese Society of Pharmaceutical Health Care and Sciences), Board certified Local Pharmaceutical
Health Care Specialist (The Japanese Society of Pharmaceutical Health Care and Sciences)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 28

Ensuring Capacity for Awareness Raising and Education
Scope: People involved in human healthcare, nursing care, public welfare, and foodPromote activities of the infectious disease education professional network (Infectious Disease Education
Consortium) by experts in each field in order to promote educational and awareness-raising activities
through collaboration among various fields (related professional associations, academic societies, local
governments, etc.)

Scope: Workers engaged in healthcare, nursing care, and public welfare, and local government officers
Provide information and promote awareness and education centered on the AMR Clinical ReferenceCenter (AMRCRC)

Scope: Workers engaged in veterinary medicine, livestock and aquaculture, agriculture, and foodImprove a platform to provide information regarding antimicrobial resistance (AMR) in the veterinary
medicine, livestock, aquaculture and agriculture fields

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Education, Culture, Sports, Science and Technology (MEXT); Ministry of Health, Labour andWelfare (MHLW); Ministry of Agriculture, Forestry and Fisheries (MAFF); National Institute of Infectious
Diseases (NIID); National Veterinary Assay Laboratory (NVAL); National Agriculture and Food Research
Organization (NARO); Food and Agricultural Materials Inspection Center (FAMIC); and National Center for
Global Health and Medicine (NCGM)EVALUATION INDICESTypes and performance of seminars and training conducted

Numbers of qualifications which require training related to antimicrobial resistance (AMR)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 29

GOAL 2CONTINUOUSLY MONITOR ANTIMICROBIALRESISTANCE AND USE OF ANTIMICROBIALS, AND
APPROPRIATELY UNDERSTAND THE SIGNS OF
CHANGE AND SPREAD OF ANTIMICROBIALRESISTANCE

Strategies(2.1)

Strengthen the Surveillance of Antimicrobial Resistance in
Healthcare and Nursing Care

(2.2)

Monitor the Trend of the Antimicrobial Use at Medical
Institutions(2.3)

Strengthen Antimicrobial Resistance Surveillance in the
Fields of Veterinary Medicine, Livestock and Aquaculture,
etc.

(2.4)

Standardize Methods of Laboratory Testing and Strengthen
Testing Functions of Antimicrobial Resistance at Clinical,
Commercial and Public Health Laboratories(2.5)

Implement Integrated One Health Surveillance Including
Humans, Animals, Food, and the Environment

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 30

STRATEGY 2.1

STRENGTHENTHESURVEILLANCEOF
ANTIMICROBIAL RESISTANCE IN HEALTHCARE
AND NURSING CAREBACKGROUND Japan recognizes the importance of surveillance on antimicrobial resistance (AMR) and has systems dedicatedto the surveillance in healthcare: the Japan Nosocomial Infections Surveillance (JANIS) which monitors thetrends of antimicrobial resistance (AMR) and the National Epidemiological Surveillance of Infectious Diseases
based on the Act on Prevention of Infectious Diseases and Medical Care for Patients Suffering Infectious
Diseases (Act No. 114 of 1998) and the nationwide computerized tuberculosis (TB)surveillance system which
tracks trends in antimicrobial-resistant Mycobacterium tuberculosis (MTB) bacteria, and the Japan Surveillance
for Infection Prevention and Healthcare Epidemiology (J-SIPHE) established in April 2017 to consolidate
antimicrobial resistance (AMR)-related data for use by medical institutions and regional networks. In addition,
the revision of medical fee in FY2022 established the premium for enhanced surveillance to evaluate medical
institutions that participate in regional and national surveillance.
 However, the prevalence of certain antimicrobial-resistant organisms (AROs) is not monitored because none of
the systems is applied for these antimicrobial-resistant organisms (AROs) and whose spread has not been fully
confirmed. 40 Japan Nosocomial Infections Surveillance (JANIS) is a voluntary survey, and most of theparticipating facilities are relatively large medical institutions with more than 200 beds, 41 but elderly carefacilities do not participate. Therefore, the challenge is to understand the actual situation of antimicrobial
resistance (AMR) in medical institutions with less than 200 beds.
Regarding healthcare-associated infection (HAI) surveillance, in addition to the Japan Nosocomial Infections
Surveillance (JANIS), the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE)42
is expected to collect and consolidate information on the medical examination status of infection diseases, infection
control measures and appropriate use of antibiotics at participating facilities, the occurrence of healthcare-associatedinfections (HAIs), major bacteria and antimicrobial-resistant organisms (AROs), bloodstream infections caused bythem, and antibiotic use, and to use this information for collaboration among individual facilities and facilities in
the region. On the other hand, the lack of participating facilities is an issue, and opportunities for utilization needs
to be increased.

 The impact of coronavirus infectious disease, emerged in 2019 (COVID-19) on the number of patients andisolation rates of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae,
and Pseudomonas aeruginosa in 2019 and 2020 were compared using the Japan Nosocomial Infectious
Surveillance (JANIS) data. The number of patients and isolation rates for each bacteria decreased slightly formethicillin-susceptible and resistant Staphylococcus aureus, decreased by 60% for penicillin-susceptible andresistant Streptococcus pneumoniae, and increased for third-generation cephalosporin-resistant Klebsiellapneumoniae. For the remaining bacteria, the number of patients decreased but the isolation rate increased. 43 

40 Thenational systems do not collect data on certain antimicrobial-resistant organisms (AROs), including multidrugresistant Neisseria gonorrhoeae, antimicrobial-resistant tuberculosis, and fluoroquinolone-resistant species in Salmonella
and Shigella. Multidrug-resistant Neisseria gonorrhoeae and antimicrobial-resistant Mycobacterium tuberculosis (MTB)
have been monitored by individual research groups.
41 Among the total of 3,016 medical institutions participating in Japan Nosocomial Infectious Surveillance (JANIS), 177
organizations submitted their data on intensive care units(ICUs), 120 organizations on neonatal intensive care units (NICUs),
and 945 organizations on surgical site infections (SSIs), as of January 2023.
42 Among the total of 1,870 medical institutions (excluding clinics) participating in Japan Surveillance for Infection Preventionand Healthcare Epidemiology (J-SIPHE), 866 organizations participate in the antimicrobial stewardship team (AST) unit,
1,730 organizations in the antimicrobial use (AMU) unit, 1,240 organizations in the infection control team (ICT) unit, 1,069
organizations in the healthcare-associated infection (HAI) unit, and 1,441 organizations in the Microorganisms andResistant Bacteria unit as of January 2023.
43 Hirabayashi A, Kajihara T, Yahara K, et al. Impact of the COVID-19 pandemic on the surveillance of antimicrobial
resistance J Hosp Infect. 2021 Nov;117:147-156. doi: 10.1016/j.jhin.2021.09.011. Epub 2021 Sep 22.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 31

POLICIES Strengthen the surveillance of antimicrobial resistance (AMR) in the medical field through reviewing andexpanding target facilities and subjects of the "Japan Nosocomial Infection Surveillance (JANIS)" to work
towards understanding the trend of antimicrobial resistance (AMR) in small medical institutions and clinics
with less than 200 beds. Particularly consider notifiable disease surveillance for antimicrobial-resistant
Mycobacterium tuberculosis (MTB), antimicrobial-resistant Neisseria gonorrhea infections and understanding
antimicrobial-resistant (AMR) fungi, which are spreading globally and becoming an issue. Work towards understanding the trend of antimicrobial resistance (AMR) among residents of small medical
institutions and elderly care facilities by reviewing target facilities and subjects of Japan Nosocomial Infections
Surveillance (JANIS).
 Develop efficient healthcare-associated infection (HAI) surveillance methods, which are based on physicians’
consultations. Link data obtained from the healthcare-associated infection (HAI) surveillance with data fromJapan Nosocomial Infections Surveillance (JANIS) and antimicrobial use (AMU) data from receipt informationby using Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) to promoteassessment and management of the risk of healthcare-associated infections (HAIs) caused by antimicrobialresistant organisms (AROs) within hospitals and regional networks.
 Strengthen comprehensive think-tank function regarding antimicrobial resistance (AMR), including collectionof various information on antimicrobial resistance (AMR) inside and outside Japan, provision of theinformation to the forefront clinicians and researchers, and policy recommendation to the government andinternational organizations such as the World health Organization (WHO)

ACTIONSStrengthen the National Epidemiological Surveillance of Infectious Diseases

Promote monitoring of antimicrobial-resistant Mycobacterium tuberculosis (MTB) and multidrug-resistant
Neisseria gonorrhoeae infections, etc.
Standardize the methods and subjects of antimicrobial susceptibility testingConduct molecular epidemiological research on multidrug-resistant Neisseria gonorrhoeaeDiscuss the necessity and relevance of notifiable disease surveillance of antimicrobial-resistant (AMR)
Pseudomonas aeruginosa infections

Implement supportive measures to facilitate the mandatory reporting on infectious diseases Support the development and introduction of a disease notification support system for electronic medical
records

Support and standardize full digitalization of reporting of medical institutions to public health centersPromote data link with the data collected by Japan Nosocomial Infections Surveillance (JANIS) regarding
antimicrobial-resistant infections (ARIs) 44 , which are included in Category V infectious diseases, andinfectious diseases facing the problem of antimicrobial resistant (AMR), and review reporting standards,
as appropriate Discuss methods to provide feedback on the risk assessment results to the local health laboratories, publichealth centers, etc. after National Institute of Infectious Disease conduct risk assessment on antimicrobial
resistance (AMR) in each region based on the notifications of infections and the data of pathogens from
National Epidemiological Surveillance of Infectious Diseases 

Strengthening the Japan Nosocomial Infections Surveillance (JANIS)

Conduct research to aid the review of target facilities and subjects of Japan Nosocomial Infections
Surveillance (JANIS) (see Strategy 3.1) 

44

Carbapenem-Resistant Enterobacteriaceae (CRE) infection, antimicrobial-resistant Acinetobacter infection,
antimicrobial-resistant Pseudomonas aeruginosa, vancomycin-resistant Enterococci (VRE) infection, vancomycin-resistant
Staphylococcus aureus infection, penicillin-resistant Streptococcus pneumoniae infection, methicillin-resistant
Staphylococcus aureus infection

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 32Support implementation of antimicrobial resistant (AMR) surveillance in medical institutions without an
in-house clinical microbiological laboratory, in partnership with off-site contract laboratories for testing Further expand targets of surveillance to include bacteria required according to the updated specificationsof the World Health Organization (WHO) Global Antimicrobial Resistance Surveillance System (GLASS)45



Accelerate data collection and analysis on key antimicrobial-resistance genes (ARGs) 46 and clinicalinformation Consider adding antimicrobial-resistant (AMR) fungi47 to the scope of the Japan Nosocomial Infections
Surveillance (JANIS)  Standardize the methods and subjects of antimicrobial susceptibility testingIntroduce a system to analyze Japan Nosocomial Infections Surveillance (JANIS) data at the regional
level 48 and promote the application of Japan Nosocomial Infections Surveillance (JANIS) data tosurveillance activities through the Regional Network for Infectious Diseases Prevention and Control(tentative name) (see Strategy 3.1) 

Enhancement of the Japan Surveillance for Infection Prevention and Healthcare
Epidemiology (J-SIPHE)

Continue to conduct surveillance through the Japan Surveillance for Infection Prevention and Healthcare
Epidemiology (J-SIPHE) in addition to the Japan Nosocomial Infections Surveillance (JANIS)  Conduct collection of healthcare-associated infection (HAI) data as part of the work of the antimicrobial
stewardship team (AST) in medical institutions and regions
 Consider investigating the disease burden, including the number of patients, deaths, disability-adjusted
life years (DALYs), quality-adjusted life years (QALYs), and other economic burden, including
treatment costs, of bloodstream infections caused by antimicrobial-resistant organisms (AROs)

Conduct study on automated system to detect suspected healthcare-associated infection (HAI) carriers
symptoms from electronic medical records (see Strategy 4.1) Conduct analysis by linking healthcare-associated infection (HAI) data with Japan Nosocomial Infections
Surveillance (JANIS)49

Provide training to provide necessary knowledge and techniques to implement Japan Surveillance for
Infection Prevention and Healthcare Epidemiology (J-SIPHE) (see Strategy 1.2 and Strategy 3.3) 

Establish a Comprehensive Think-tank Organization for Antimicrobial Resistance (AMR)Strengthen antimicrobial resistance (AMR) control measures from basic research to clinical through thecollaboration between the Antimicrobial Resistance Research Center in the National Institute of Infectious
Diseases (NIID) and the AMR Clinical Reference Center (AMRCRC) of the National Center for Global
Health and Medicine (NCGM) 

45 Strains(Acinetobacter spp., E. coli, K. pneumoniae, P. aeruginosa, S. aureus, S. pneumoniae, N. meningitidis, H.
influenzae, Salmonella spp.(non-typhoidal), S. enterica serovar Typhi, S. enterica serovar Paratyphi A, Shigella spp., N.
gonorrhoeae), Specimen information (blood, CSF spinal fluid, urine, stool, and lower respiratory tract-derived specimens),
antimicrobial resistance factors (NDM, OXA, VIM, IMP, GES, KPC, mcr 1-10, CTX-M, TEM, SHV, NDM, OXA, VIM,
mecA/mecC, cfr)
46 Includes genes for extended-spectrum beta-lactamases (ESBL), third-generation cephalosporin resistance such as
AmpC, metallo-beta-lactamase (MBL), carbapenemases such as KPC and OXA, and other important antimicrobial
resistance such as MCR-1
47 Candida albicans; C. glabrata; C. parapsilosis; C. tropicalis; C. krusei
48 A system to analyze Japan Nosocomial Infections Surveillance (JANIS) data at the regional level has already been
designed through the development of a Regional Infection Control Support System (mentioned below), supported by the
Health and Labour Sciences Research Grants (Grants-in-aid for Scientific Research).
49 The Regional Infection Control Support System is designed to enable the collaboration with Japan Nosocomial Infections
Surveillance (JANIS). By interchanging its data with healthcare-associated infection (HAI) surveillance data, the System
can identify the antimicrobial-resistant organisms (AROs) that contribute to cause healthcare-associated infections (HAIs)
and analyze the degree thereof.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 33

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); National Institute of Infectious Diseases (NIID); National
Center for Global Health and Medicine (NCGM); public health centers; and prefectural and municipal publichealth institutes

EVALUATION INDICES


Number of reports on antimicrobial-resistant Mycobacterium tuberculosis (MTB), multidrug-resistant
Neisseria gonorrhoeae infections, etc.



Number of medical institutions participating in antimicrobial resistance (AMR) surveillance and its
research

Table 7. Major Healthcare-associated Infections (HAIs) (the surveillance targets of the U.S. Centers for
Disease Prevention and Control)
Healthcare-associated Infections (HAIs)
Central line-associated
Bloodstream Infections(CLABSIs)

Bacteraemia and sepsis triggered by infection in central line-associated bloodstream, andtheir complications

Catheter-associated Urinary Tract Urinary tract infections developed in patients with a urinary catheter, including bladder
Infections (CAUTIs)
catheterization
Ventilator-associated(VAP)

Pneumonia Pneumonia developed in patients using a medical ventilator

Surgical Site Infections (SSIs)

Infections developed at surgical sites after operation

Clostridium difficile Infections(CDIs)

Enteral infections caused by Clostridium difficile(CDIs may be facilitated by selective proliferation of the strain by antibiotic use.)

Reference: The U.S. Centers for Disease Prevention and Control (National Healthcare Safety Network and Emerging Infections Program)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 34

STRATEGY 2.2

MONITOR THE TREND OF THE ANTIMICROBIAL
USE AT MEDICAL INSTITUTIONSBACKGROUND

Antimicrobial use (AMU) in medical institutions is known to be closely associated with antimicrobial resistance(AMR). 50 It is demonstrated that reduction of antimicrobial use (AMU) represses the emergence ofantimicrobial-resistant organisms (AROs).51

 Antimicrobial use (AMU) surveillance in medical institutions leads to understand antimicrobial use (AMU)
indicators52, and conduct quantitative and qualitative evaluation of antimicrobial stewardship (AMS) between
medical institutions by linking antimicrobial resistance (AMR) surveillance data collected by Japan
Nosocomial Infections Surveillance (JANIS), and research on utilization of antimicrobial use (AMU)
surveillance has been conducted.53
 Furthermore, using the antimicrobial use (AMU) indicators, which are of international standards, enables
comparison of antimicrobial use (AMU) status in Japan with the world.
 Considering that antimicrobial use varies by region as well as dosage and number of days of administration
depending on the type of infection, patient age, organ function, etc., it is necessary to develop a system thatenables detailed trend monitoring at each medical institution.
 Currently, inpatient and outpatient monitoring of antimicrobial use (AMU) using sales volume and medicalbilling information.54 The results of this survey revealed that antimicrobial prescriptions are used more in clinics
than in hospitals. In particular, 90% of prescriptions are for outpatient use, and it has become clear that many
antibiotics are used for diseases such as upper respiratory tract infections and diarrhea, which are not considered
to require antibiotics.55,56,57 In order to further promote appropriate use, it is important to conduct a surveillancetargeting clinics where a large number of prescriptions are made.
 The online monitoring system for antimicrobial stewardship at clinics was established to promote theantimicrobial stewardship (AMS) at clinics by analyzing and visualizing information on antimicrobial
prescriptions and names of injuries and diseases at clinics nationwide, and to consolidate and utilize informationon the status of antibiotic use at participating medical institutions and in local networks. Although a Point
Prevalence Survey (PPS) on antibiotic use was conducted in health care facilities for the elderly requiring longterm care, participation has been limited to a small number of facilities, and it is necessary to expand the numberof participating facilities.


50 Bell BG, Schellevis F, Stobberingh E, Goossens H, Pringle M. A systematic review and meta-analysis of the effects ofantibiotic consumption on antibiotic resistance. BMC Infect Dis. 2014;14:13. Published 2014 Jan 9. doi:10.1186/1471-233414-13
51 Dancer SJ, Kirkpatrick P, Corcoran DS, Christison F, Farmer D, Robertson C. Approaching zero: temporal effects of a
restrictive antibiotic policy on hospital-acquired Clostridium difficile, extended-spectrum β-lactamase-producing coliforms
andmeticillin-resistant
Staphylococcus
aureus.
Int
J
Antimicrob
Agents.
2013;41(2):137-142.
doi:10.1016/j.ijantimicag.2012.10.013
52 The combination of antimicrobial use density (AUD) , the days of therapy (DOT) and their combination
53 2021 Health and Labour Sciences Research Grant, Research on Implementation of National Action Plan on Antimicrobial
Resistance (AMR)
54 Japan Surveillance of Antimicrobial Consumption (JSAC)
http://amrcrc.ncgm.go.jp/surveillance/010/ref/NDB_2013-2020.pdf
55 Hashimoto H, Saito M, Sato J, et al. Indications and classes of outpatient antibiotic prescriptions in Japan: A descriptive
study using the national database of electronic health insurance claims, 2012-2015. Int J Infect Dis. 2020;91:1-8.
doi:10.1016/j.ijid.2019.11.009
56 Kimura Y, Fukuda H, Hayakawa K, et al. Longitudinal trends of and factors associated with inappropriate antibiotic
prescribing for non-bacterial acute respiratory tract infection in Japan: A retrospective claims database study, 2012-2017.
PLoS One. 2019;14(10):e0223835. Published 2019 Oct 16. doi:10.1371/journal.pone.0223835
57 Ono A, Aoyagi K, Muraki Y, et al. Trends in healthcare visits and antimicrobial prescriptions for acute infectious diarrhea
in individuals aged 65 years or younger in Japan from 2013 to 2018 based on administrative claims database: aretrospective observational study. BMC Infect Dis. 2021;21(1):983. Published 2021 Sep 21. doi:10.1186/s12879-02106688-2

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 35

 Antimicrobial use (AMU) had been gradually decreasing since 2016, with an even larger decrease starting in
2020.58 The reduction in the incidence of acute respiratory tract infections and the number of patients seen inclinics as a result of infection control measures taken against Corona Virus Infectious Disease, emerged in 2019
(COVID-19) may have contributed to decrease antimicrobial use (AMU). Preventive measures against
infections in addition to the antimicrobial stewardship (AMS) contributed to the reduction of antimicrobial use(AMU).

POLICIESDevelop surveillance methods to monitor antimicrobial use (AMU) in medical institutions (inpatient andoutpatient departments)

 Monitor antimicrobial use (AMU) indicators at individual medical institutions, and conduct quantitative andqualitative comparison and evaluation of antimicrobial stewardship (AMS) continually by linking antimicrobialuse (AMU) indicators with antimicrobial resistance (AMR) surveillance data from Japan Nosocomial Infections
Surveillance (JANIS)
 Monitor the actual status of antimicrobials prescribed in nursing care facilities

ACTIONS

Antimicrobial Use Surveillance in Medical Institutions by Japan Surveillance for Infection
Prevention and Healthcare Epidemiology (J-SIPHE)

Promote participation of small and medium-sized hospitals and clinics in the Japan Surveillance for
Infection Prevention and Healthcare Epidemiology (J-SIPHE). Enhance utilization through collaboration
with Japan Nosocomial Infections Surveillance (JANIS) Promote securing a system capable of a quantitative and qualitative evaluation using Japan Surveillance
for Infection Prevention and Healthcare Epidemiology (J-SIPHE), etc. in the framework between medical
institutions, etc., and consider a method to feed back the multicenter comparisons to each medical
institution.
Promote utilization of the antimicrobial use (AMU) surveillance system in hospital outpatient departments
and clinics Promote utilization of the National Database for Prescription and National Health Check-up (NDB) 

Encourage participation of medical institutions in the antimicrobial use (AMU) surveillance system Conduct research on the integration of antimicrobial use (AMU) surveillance systems in inpatient andoutpatient departments Conduct research studies to explore infection incidence, antimicrobial use rates, descriptions of prognosis
and risk factors for each department Explore collaboration of the antimicrobial use (AMU) surveillance systems between inpatient andoutpatient departments 

Apply Antimicrobial Use (AMU) Surveillance to Risk Assessment and Risk Management
Continue quantitative and qualitative evaluation of antimicrobial stewardship (AMS) (benchmarking) inindividual medical institutions, and conduct research studies for utilization of antimicrobial stewardshipby linking antimicrobial use (AMU) indicators of some medical institutions with Japan Nosocomial
Infections Surveillance (JANIS) data (see Strategy 4.1) Revise guidelines to evaluate the quality of antimicrobial stewardship (AMS) using antimicrobial use(AMU) indicators 
58 Japan Surveillance of Antimicrobial Consumption (JSAC)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 36Promote securing a system capable of quantitative and qualitative evaluation using antimicrobial use(AMU) indicators in the framework in the Regional Network for Infectious Diseases Prevention andControl (tentative name) (see Strategy 3.1), between medical institutions, etc., and consider a method tofeed back the multicenter comparisons to each medical institution. Enhance the "One Health Platform for Antimicrobial Resistance (AMR)" with information on
antimicrobial use, antimicrobial resistance rates, information on medical practices59, and other informationin each prefecture, using Japan Surveillance for Infection Prevention and Healthcare Epidemiology (JSIPHE) and Japan Nosocomial Infections Surveillance (JANIS) data

Monitor the Actual Status of Antimicrobial Prescription in Nursing Care Facilities


Monitor the use of antimicrobials prescribed in nursing care facilities 

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); National Institute of Infectious Diseases (NIID); National
Center for Global Health and Medicine (NCGM); public health centers; and prefectural and municipal publichealth institutes

EVALUATION INDICESAntimicrobial use (AMU) in medical institutions



Number of organizations participating in antimicrobial use (AMU) surveillance for inpatient andoutpatient departments

Number of local governments conducting systematic evaluation of local antimicrobial use (AMU)
indicators

59 The examples are: blood culture status (multiple set rate), hand hygiene use/adherence rate

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 37

STRATEGY 2.3

STRENGTHEN ANTIMICROBIAL RESISTANCESURVEILLANCE IN THE FIELDS OF VETERINARY
MEDICINE, LIVESTOCK AND AQUACULTUREBACKGROUNDIn 1999, the Government of Japan started a system to monitor nation-wide trends of antimicrobial resistance(AMR) in livestock, called the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM),
and its core laboratory, the National Veterinary Assay Laboratory (NVAL), conducts surveillance ofantimicrobial-resistant organisms (AROs) in partnership with prefectures, the Food and Agricultural Materials
Inspection Center (FAMIC), and other organizations. For its part, it collects data on antimicrobial use (AMU)
converted from sales volume of antibiotics for animals, and the results are published annually, and data isprovided to the "Nippon AMR One Health Report (NAOR)" from the perspective of the One Health approach.
Furthermore, it is provided as Japanese data to "the Annual Report on Antimicrobial Agents Intended for Usein Animals" compiled and reported by the World Organisation for Animal Health (WOAH).



Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) conducts survey and research including
characterization of various antimicrobial-resistant organisms (AROs) and uses the results as the basis for risk
assessment. In order to accumulate and analyze genetic information on antimicrobial resistant bacteria, thegenome database (J-VEG) was newly developed in FY2019, and some data was registered to start analysis. In
the future, the database should be further enhanced and accurately detect warning signs of changes andexpansion of antimicrobial resistance (AMR).



The Food and Agricultural Organization of the United Nations (FAO) considers that antimicrobial-resistantbacteria of aquacultural origin have a minor impact on human health.60 Organized surveillance and monitoring
systems are not seen overseas in this field. On the other hand, in Japan, surveillance has been conducted on theantimicrobial susceptibility of pathogens that are target of efficacy or effects of antibiotics for farm-raised
aquatic animals, and the surveillance has been used as a basis for risk assessment.

In the field of pets, there has been no international surveillance and monitoring of antimicrobial susceptibility,
except in some European countries, but in Japan, surveillance of antimicrobial susceptibility in diseased pets
started in 2017 and in healthy pets in 2018.

In the field of agriculture, the Food and Agriculture Organization of the United Nations (FAO) and otherorganizations are discussing the collection and sharing of data related to surveillance.

POLICIES
Continue surveillance on antimicrobial resistance (AMR) in livestock, farm-raised aquatic animals, and petsContinue surveillance to estimate the use of antimicrobials used in animal and agriculture fields



Make outcomes of these efforts widely known. Apply the outcomes for risk assessment and the One Health
Surveillance, described in Strategy 2.5. Use them also to develop risk management measures Enhance the database of antimicrobial-resistance genes (ARGs) and other genes in the animal field to accurately
identify warning signs of changes and expansion of antimicrobial resistance (AMR)

ACTIONS

Implement Surveillance on Antimicrobial Resistance (AMR) in Animal Fields
Enhance the surveillance of antimicrobial resistance (AMR) in livestock, farm-raised aquatic animals, andpets, while reviewing target species and drugs in a timely and appropriate manner Develop antimicrobial susceptibility testing manuals, etc. to enable harmonised comparison and evaluationand collect data based on the uniform methods

60 Improving biosecurity through prudent and responsible use of veterinary medicines in aquatic food production, FAO

Fisheries and Aquaculture Technical Paper No. 547, 2012.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 38







Perform whole genome analysis on the collected strains and continue to accumulate gene informationImplement Surveillance on Antimicrobial Use (AMU)Continue surveillance to estimate the antimicrobial use (AMU) of antibiotics for animals in livestock,farm-raised aquatic animals, and petsContinue surveillance to estimate the antimicrobial use (AMU) of human antibiotics in livestock and pets Newly establish a system to understand the antimicrobial use (AMU) per farm in the livestock field Continue surveillance to estimate the antimicrobial use (AMU) of antibiotic feed additives per target
livestock Implement surveillance on the antimicrobial use (AMU) in agricultureApplication of Surveillance to Risk Assessment and Risk Management
Adequately identify warning signs of change or spread of antimicrobial resistance (AMR) based on thestatus of antimicrobial resistance (AMR) in different livestock species and outbreaks of livestock diseasesAnalyze the epidemiological relationship between zoonotic and human-derived antimicrobial-resistantbacteria in collaboration with the Japan Nosocomial Infections Surveillance (JANIS), using the results ofwhole genome analysis of strains collected by the Japan Veterinary Antimicrobial Resistance Monitoring(JVARM)

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Agriculture, Forestry and Fisheries (MAFF); NVAL, National Agriculture and Food Research
Organization (NARO); FAMIC; Fisheries Research Agency (FRA); livestock hygiene service centers; andfisheries research and laboratory facilities

EVALUATION INDICES


Number of surveillance reports

Number of obtained strains

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 39

STRATEGY 2.4

STANDARDIZE METHODS OF LABORATORYTESTINGAND
STRENGTHENTESTINGFUNCTIONS OF ANTIMICROBIAL RESISTANCE AT
CLINICAL, COMMERCIAL AND PUBLIC HEALTHLABORATORIESBACKGROUND
 Antimicrobial resistance (AMR) testing includes pathogen culture and identification, antimicrobial
susceptibility testing, nucleic acid amplification tests, antimicrobial-resistance gene (ARG) tests, andantimicrobial resistance (AMR) rapid diagnosis kits. Epidemiological genome analysis is used to study
antimicrobial-resistant infection (ARI) outbreaks. However, quality control measures have not uniformly been
applied nationwide to these tests, posing obstacles to the implementation and evaluation of antimicrobial
resistance (AMR) surveillance and monitoring. The number of laboratories capable of conducting detailed
analysis on antimicrobial resistance (AMR) including antimicrobial-resistance gene (ARG) is still limited, andexamination standards, targets, and methods used among them are not standardized.
 In the field of animals, in order to unify the methods used by inspection organizations that participate in the"Japanese Veterinary Antimicrobial Resistance Monitoring (JVARM)" investigation, the National Veterinary
Assay Laboratory (NVAL), the core laboratory, has provided training to prefectural livestock health inspectors
and quality control to inspection organizations.
 In-house clinical microbiological laboratories play significant roles in antimicrobial resistance (AMR) andhealthcare-associated infection (HAI) surveillance and monitoring, and antimicrobial stewardship (AMS).
However, examination in medical institutions, particularly microbial examination, have been considered
unprofitable. Therefore, many small and medium-sized hospitals have chosen to outsource such testing.

POLICIES


Endeavor to improve the level of test technologies and ensure the availability of an examination system forstandardized comparison and evaluation by supporting the establishment of nation-wide, external evaluation
management systems for antimicrobial resistance (AMR) tests

The National Veterinary Assay Laboratory (NVAL), which is the core laboratory, conducts training and quality
control to improve the accuracy of laboratory testing techniques and ensure an examination system that enables
unified comparison and evaluation.

Conduct research on microbial examination systems, which aims to enhance antimicrobial stewardship (AMS)
in medical institutions Explore the possibilities of introducing new technologies and equipment in public and animal healthlaboratories61 to enhance their capacity of antimicrobial resistance (AMR) related information collection andprovision

ACTIONSStandardize Testing Methods and Strengthen Quality Control


Renew the antimicrobial susceptibility testing manual in line with the international standards, whichenables harmonised comparison and evaluation in each field and implement training using the manual Support the establishment of external evaluation management systems and promote the introduction of thesystem in medical institutions and laboratories 
61 Public and animal health laboratories include the National Institute of Infectious Diseases (NIID), the National Veterinary

Assay Laboratory (NVAL), prefectural and municipal public health institutes, and livestock hygiene service centers

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 40







Develop manuals and guidelines for testing antimicrobial-resistance genes (ARGs) and comparative
analysis of antimicrobial-resistant organisms (AROs) Consider creating bacterial strains (panels) to be used for quality control of bacteriological assay
instruments and providing them to laboratories nationwide, and promote public awareness of them

Renew the manuals and guidelines for each medical institution to create an antimicrobial susceptibility
table (e.g. antibiogram) of major causative microorganisms Continuously implement training, quality control, etc. in order to conduct tests using unified methods at
inspection organizations involved in investigation by the Japanese Veterinary Antimicrobial Resistance
Monitoring System (JVARM) 

Expand Testing Capacity related to Antimicrobial Resistance and Conduct Research for the
PurposeStrengthen and expand the capacity of antimicrobial resistance (AMR) related information collection andprovision in public and animal health laboratoriesConduct clinical research on the use of antimicrobial resistance (AMR)-related tests62 and basic microbial
tests63, which may contribute to enhance antimicrobial stewardship (AMS) (see Strategy 5.2) Introduce New Technologies for Surveillance and Monitoring and Apply Them to Control
Measures

Develop new technologies 64 for surveillance and monitoring based on molecular epidemiology andpromote their introduction in public and animal health laboratories Strengthen surveillance and monitoring 65 based on molecular epidemiology by expanding theantimicrobial resistance (AMR) genome database and apply the outcomes to risk assessment and risk
management 

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); Ministry of Agriculture, Forestry and Fisheries (MAFF);
National Institute of Infectious Diseases (NIID); National Veterinary Assay Laboratory (NVAL); National
Agriculture and Food Research Organization (NARO); Food and Agricultural Materials Inspection Center(FAMIC); National Center for Global Health and Medicine (NCGM); public health centers; prefectural andmunicipal public health institutes; and livestock hygiene service centers

EVALUATION INDICES


Number of organizations adopting standards



Number of training seminars implemented for standardization

Number of samples obtained from surveillance and monitoring based on molecular epidemiology

62 Antimicrobial resistance (AMR)-related tests include: E-test, Break-point Checkerboard Plate method, multiplex PCR,

rapid detection test for antimicrobial-resistant gene products, matrix-assisted laser desorption/ionization time of flight mass
spectrometry (MALDI-TOF MS).
63 Basic microbial tests include: Gram staining, fluorescent labeling, bacterial culture and identification, anaerobic culture
test, bacterial antimicrobial susceptibility testing, acid-fast bacilli culture test, acid-fast bacilli antimicrobial susceptibility
testing, yeast-like fungus antifungal susceptibility testing, rapid diagnosis of various bacteria and viruses
64 New technologies for surveillance and monitoring based on molecular epidemiology include: Whole genome sequencing(WGS), and metagenomic analysis.
65 Elucidate the transmission pathways of antimicrobial-resistance genes (ARGs) and antimicrobial-resistant organisms(AROs) by interchanging data from antimicrobial-resistant organism (ARO) genome analysis, genome database, andsurveillance and monitoring. Apply the findings for developing control measures.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 41

STRATEGY 2.5

IMPLEMENTINTEGRATEDONEHEALTHSURVEILLANCE INCLUDING HUMANS, ANIMALS,
FOOD, AND THE ENVIRONMENTBACKGROUND
 Accurate understanding of the antimicrobial resistance (AMR) ecosystem - the variety, spread, and transmission
pathways - is essential for eliminating the transmission pathways of antimicrobial resistance (AMR).
 Japan currently has two antimicrobial resistance (AMR) surveillance and monitoring systems, the Japan
Nosocomial Infections Surveillance (JANIS) for human health and the Japanese Veterinary Antimicrobial
Resistance Monitoring System (JVARM) for animal health, and their collaboration has been promoted. On food,research has been conducted on multidrug-resistant Enterobacteriaceae and Vancomycin-resistant Enterococci,
and data on antimicrobial resistance (AMR) in bacteria of food origin collected by prefectural and municipal
public health institutes has been linked with the data from Japan Nosocomial Infections Surveillance (JANIS)
and Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) and checked on a regular basis.
 In addition, the antimicrobial resistance (AMR) One Health Platform is operated at the AMR Clinical ReferenceCenter (AMRCRC) to consolidate information on One Health-related AMR, antimicrobial use (AMU) ininpatient and outpatient departments, infectious diseases, and vaccination in order to utilize this information
for antimicrobial resistance (AMR) control in each region. This facilitates the use of the data of antimicrobial
resistance (AMR) not only in the human field, but also in livestock, farm-raised aquatic animals, and pets.
 Furthermore, in order to examine the status of the antimicrobial use (AMU) for humans and animals and theantimicrobial resistance rates of microorganisms in Japan, the "Antimicrobial Resistance One Health
Surveillance Committee" was established and experts in the fields of humans, animals, food and theenvironment discuss them. The committee prepares the annual "Nippon AMR One Health Report (NOAR)" toevaluate the current status and understanding of trends in antimicrobial resistance (AMR) and antimicrobial use(AMU) in each field in Japan.

POLICIES Data will be consolidated and shared in the network established by the National Institute of Infectious Diseases(NIID), the National Veterinary Assay Laboratory (NVAL), and the National Center for Global Health andMedicine (NCGM) to establish the One Health Surveillance system with world-wide actions beyond barriers
between humans and animals, etc., which links data from multiple surveillance and monitoring systems
including the Japan Nosocomial Infections Surveillance (JANIS) and Japanese Veterinary Antimicrobial
Resistance Monitoring System (JVARM). In addition, the "Antimicrobial Resistance One Health SurveillanceCommittee" will periodically analyze and evaluate the trend of antimicrobial resistance (AMR) andcountermeasures by coordinating information from each surveillance and monitoring, while also conducting
international comparisons. In addition, the evaluation results will be made public and utilized in the review ofthe "National Action Plan on Antimicrobial Resistance (AMR) (2023-2027)".
 Conduct research to prepare for establishing surveillance and monitoring systems of antimicrobial-resistantorganisms (AROs) in food Conduct research on surveillance and monitoring of antimicrobial-resistant organisms (AROs) and residual
antimicrobials in aquatic and terrestrial environment, as well as in wild animalsNational Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 42

Humans

Pets

The EnvironmentFood

One HealthApproach

Aquaculture

Wild animals

Agriculture
Livestock

Figure 6 Collaboration under One Health approach

ACTIONS

Promote the One Health Surveillance System


Implement the following measures at the Antimicrobial Resistance One Health Surveillance Committee 66
for antimicrobial resistance (AMR) and antimicrobial use (AMU);


Create the One Health Surveillance Network on Antimicrobial Resistance (AMR) (tentative name),
which includes National Institute of Infectious Diseases (NIID), National Veterinary Assay Laboratory(NVAL), National Center for Global Health and Medicine (NCGM) and conduct collecting and sharing dataContinue to promote the analysis and evaluation based on the integrated data from surveillance andmonitoring, other scientific studies, and tests conducted by local governments

Continue preparation and publication of the annual "Nippon Antimicrobial Resistance One HealthReport (NAOR)"67 and improve the contents

Conduct research to prepare for establishing an antimicrobial resistance (AMR) surveillance andmonitoring system on food68



Analyze transmitting factors of antimicrobial resistance (AMR) in humans, animals, food, and environment.
Conduct research to elucidate linkage between their transmission processes Conduct research to monitor antimicrobial resistance (AMR) and residual antimicrobials in aquatic andterrestrial environment Collect information on antimicrobial-resistant bacteria, including their presence in the environmental
water and soil and their impact on health Collect basic information on residual antimicrobials in the environment Link data related to antimicrobial resistance (AMR) surveillance/monitoring across humans, animals, food,and environment, and conduct investigation and analysis of antimicrobial-resistant bacteria that are feared
to be transmitted to humans using genetic databasesImplement surveillance on the antimicrobial use (AMU) in agriculture

Modify the national surveillance and monitoring projects to align with changes to the Global Antimicrobial
Resistance Surveillance System (GLASS) Conduct surveillance and monitoring in each region regarding antimicrobial resistance (AMR) to facilitate
the use of the "AMR One Health Platform" for regional collaboration, and promote the use of the platformby posting their interpretation of data and initiatives in each region 

66 Committee members’ areas of expertise : human clinical practice, human resistant bacteria, human antibiotics, animal

resistant bacteria, animal antimicrobials, food resistant bacteria, environmental resistant bacteria, environmental residual
antibiotics
67 Nippon AMR One Health Report (NAOR) 2017, NAOR 2018, NAOR 2019, NAOR 2020, NAOR 2021
https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/0000120172.html
68 This includes imported food products.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 43

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSFood Safety Commission of Japan (FSC), Cabinet Office (CAO); Ministry of Health, Labour and Welfare(MHLW); Ministry of Agriculture, Forestry and Fisheries (MAFF); Ministry of the Environment (MOE);
National Institute of Infectious Diseases (NIID); National Veterinary Assay Laboratory (NVAL); National
Agriculture and Food Research Organization (NARO); Food and Agricultural Materials Inspection Center(FAMIC); NCGM; public health centers; prefectural and municipal public health institutes; and livestock hygiene
service centers

EVALUATION INDICESReported number on surveillance under One Health approachNumber of samples obtained by antimicrobial resistance (AMR) surveillance and research in each field

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 44

GOAL 3
PREVENT THE SPREAD OF ANTIMICROBIALRESISTANT ORGANISMS BY IMPLEMENTINGAPPROPRIATE INFECTION PREVENTION AND
CONTROL

Strategies(3.1)

Infection Prevention and Control in Healthcare and Nursing
Care and Promotion of Regional Cooperation(3.2)

Promote Infection Prevention and Control in Livestock andAquaculture, Veterinary Medicine and Food Chain(3.3)

Strengthen the Outbreak Response Capacity against
Antimicrobial-resistant Infections

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 45

STRATEGY 3.1

INFECTION PREVENTION AND CONTROL IN
HEALTHCARE AND NURSING CARE AND
PROMOTION OF REGIONAL COOPERATIONBACKGROUNDWith the amendment of the Medical Care Act (Act No. 205 of 1948) in 2006, all medical institutions became
obligated to establish a nosocomial infection control committee to promote nosocomial infection control. With
the revision of the medical fee in FY2012, a premium for regional cooperation in infection control was created
and regional infection control networks69 among medical institutions are being established to support infection
control of small and medium-sized medical institutions. With the revision of the medical fee in FY2022, thepremium for improvement of infection control measures was newly established to further promote efforts for
infection prevention and control (IPC).70



Concerning efforts that have been referred to as "infection control", the role of infection prevention has become
important, and it is being addressed in an integrated manner as "infection prevention and control (IPC)".

In the meantime, recently, as antimicrobial resistant organisms (AROs) have become a hot issue in nursing carefacilities, efforts to control healthcare-associated infections (HAIs)71 are being promoted as a broader concept.72
However, current nosocomial infection control is mainly intended for inpatient and outpatient departments ofmedical institutions, and it is not clearly stated to cover nursing care facilities.



The outbreak of Corona virus infectious disease, emerged in 2019 (COVID-19) has increased awareness of
infection prevention and control (IPC) and improved the implementation rate and techniques of hand hygiene
and wearing protective equipment.73 These results should be used to further improve the quality of nosocomial
infection control measures at medical institutions by applying them to antimicrobial resistance (AMR) control
measures as well. 

POLICIES


Promote a cooperation system in which infection prevention and control (IPC) are addressed in an integrated
manner in various clinical settings, such as inpatient and outpatient departments in medical institutions, nursing
care facilities, and home care, and promote comprehensive antimicrobial resistance (AMR) control measures,
linking the efforts of the existing infection control team (ICT) at the field level with those of antimicrobial
stewardship program (ASP)



Regarding infection prevention and control (IPC), expand activities in cooperation with regional hospitals andrelated organizations (clinics, pharmacies, nursing care facilities, public health centers, prefectural andmunicipal public health institutes, etc.), develop concrete activity models of a comprehensive regional infection
prevention and control network, and support its sequential establishment all over the countryPromote research on technical support to promote infection prevention and control (IPC) (automatic analyticalsystem of clinical data, etc.)



Enhance infection prevention and control (IPC) through promoting vaccination and utilizing the relevant
framework of medical care quality evaluation

69 There is a program of establishing a regional network for nosocomial infection control, which is intended to support theprevention and response of healthcare-associated infections. This is implemented in some prefectures.
70 Participating medical institutions in 2020 annual report were 778 institutions (eligible for the premium 1 for infection control
measures; 539, eligible for the premium 2 for infection control measures; 232, no premium; 7)
71 Strausbaugh LJ. Emerging health care-associated infections in the geriatric population. Emerg Infect Dis. 2001;7(2):268271. doi:10.3201/eid0702.010224
72 Cohen CC, Herzig CT, Carter EJ, Pogorzelska-Maziarz M, Larson EL, Stone PW. State focus on health care-associatedinfection prevention in nursing homes. Am J Infect Control. 2014;42(4):360-365. doi:10.1016/j.ajic.2013.11.024
73 Japan Surveillance for Infection Prevention and Healthcare Epidemiology （J-SIPHE） 2020/2021 Annual Report

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 46

ACTIONS

Promote Infection Prevention and Control and Strengthen Regional Cooperation
Continue to discuss infection prevention and control (IPC) measures at outpatient departments and forhome care by the "Antimicrobial resistance (AMR) Subcommittee" and the "Antimicrobial
Stewardship(AMS) Working Group" (see Stratety 4.1) established under Ministry of Health, Labour andWelfare (MHLW), as appropriate

Continue research to review target facilities and subjects to the Japan Nosocomial Infections Surveillance(JANIS) (see Strategy 2.1).



Based on the implementation of the concrete activity model of regional infection control measures,("Regional Network for Infectious Diseases Prevention and Control (tentative name))" project, consider
the role of prefectures and promote nationwide expansion of the project

Disseminate concrete application models of the premium for improvement of infection control measures,and promote more effective operation that uses Japan Surveillance for Infection Prevention and Healthcare
Epidemiology (J-SIPHE)

Conduct research to evaluate the thoroughness and compliance rate of daily hand hygiene in hospitals andother institutions

Introduce antimicrobial stewardship (AMS) and antimicrobial resistance (AMR) screening components
into the infection prevention and control (IPC) guidelines and manuals, based on current situation surveys
of antimicrobials at nursing care facilities, as appropriate (see Strategy 5.2)

Development a System of Cooperation among Laboratories, Medical Institutions, and Local
Governments

Create a reporting and consultation system for the detection of clinically important antimicrobial- resistantorganisms (AROs) at laboratories

Promote research to develop a manual for risk assessment and management on antimicrobial resistance(AMR) in cooperation with local stakeholders

Conduct comparison and evaluation (benchmarking) of infection prevention and control (IPC) at the levelof medical institutions, regions and nation, and implement research for promoting infection prevention andcontrol (IPC) measures based on the results

Promote Infection Prevention
Continue to promote vaccinations (Streptococcus pneumoniae, Heamophilus influenzae Type b (Hib),
influenza vaccines, etc.) contributing to promote the prevention of antimicrobial-resistant infections(ARIs)

Continue to promote evaluations related to infection prevention and control (IPC) and antimicrobial
stewardship (AMS), etc. in the Quality Health Care Evaluation scheme

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); National Institute of Infectious Diseases (NIID); National
Center for Global Health and Medicine (NCGM); public health centers; prefectural and municipal public healthinstitutes; Japan Council for Quality Health CareEVALUATION INDICES


Number of healthcare-associated infections (HAIs) caused by antimicrobial-resistant organisms (AROs)



Number of local goverments that have established Regional Network for Infectious Diseases Prevention
and Control (tentative name) that meets the requirements

Vaccination rates of Streptococcus pneumoniae, Haemophilus influenzae Type b (Hib), and Influenza
vaccines
National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 47

STRATEGY 3.2

PROMOTE INFECTION PREVENTION AND
CONTROL IN LIVESTOCK AND AQUACULTURE,
VETERINARY MEDICINE AND FOOD CHAINBACKGROUND

Improving the level of rearing hygiene management and maintaining the health condition of livestock areextremely important elements of controlling the occurrence and selection of antimicrobial-resistant organisms(AROs), leading to the prevention of the occurrence of infectious diseases in animals, to secure safety
production of animal products, as well as to reduce instances of using antibiotics for animals. They are also
highly important from the viewpoint of reducing production costs.

Regarding appropriate rearing hygiene management to prevent infectious diseases at the production sites ofanimal products, the biosecurity standards were established based on the provisions of the Act on Domestic
Animal Infectious Diseases Control (Act No. 166 of 1951). The status of biosecurity for the care of the livestock(cattle, pig, poultry, etc.), the implementation status of the biosecurity instruction plan, the implementation
status of instructions, advice, recommendations and orders submitted by the Prefectural Governor, and thestatus of securing prefectural livestock health inspectors are announced to the public every year by eachprefecture, to promote the improvement in the conditions of hygienic control.



Handbook for Hygienic Practice during Primary Production (beef, pork, poultry and eggs), which describes
measures to produce safer animal products as well as to reduce the occurrence of food poisoning, in addition
to measures to prevent infectious diseases in livestock provided in the biosecurity standards is publicly available.On the other hand, for appropriate hygiene management for the prevention of infectious diseases at the
production site of farm-raised aquatic animal, the "Guideline for Disease Control of Aquatic Animals" and the"Basic Plan for Fisheries" require aquaculture producers to take hygiene management measures and to use
aquaculture drugs appropriately.For food processing and distribution processes, Hazard Analysis and Critical Control Point (HACCP) became
mandatory for all businesses in principle in the revision of the Food Sanitation Act (Act No. 233 of 1947) in2018 in order to promote countermeasures to reduce contamination with antimicrobial-resistant organisms(AROs) and other microorganisms as well as to prevent food poisoning from occurring.In all fields of livestock, farm-raised aquatic animals and pets, appropriate vaccination is important to prevent
infectious diseases, in addition to thorough hygienic management. Under the present circumstances, thedevelopment of vaccines for orphan diseases and farm-raised aquatic animals is hampered due to the small
market, even if they are desired.

POLICIES


Raise and promote awareness of infection prevention and control (IPC) at facilities related to livestock andaquaculture as well as veterinary medicine through further stringent compliance with the biosecurity standards,
appropriate vaccinations, and dissemination of the Handbook for Hygienic Practice during Primary Production

Raise awareness that the prevention of infectious diseases will result in antimicrobial resistance (AMR) control,
reducing the opportunities to use antibiotics for animals

Embed Hazard Analysis and Critical Control Point (HACCP) in food processing and the distribution process

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 48

ACTIONS

Promote Infection Prevention and Control (IPC) of Livestock, Farm-raised Aquatic Animals
and PetsPromote development and commercialization of vaccines and immunostimulants for livestock, farm-raised
aquatic animals and petsEnsure compliance with the biosecurity standards based on the provisions of the Act on the Prevention of
Infectious Disease in Livestock, and disseminate the Handbook for Hygienic Practice during Primary
Production

Share good practices in the livestock field with producers, and ensure thorough guidance on the appropriate
use of antimicrobials by the officials of Livestock Hygiene Service Centers, etc.

Share good practices in rearing management with prefectural governments, and strengthen the system ofappropriate guidance on aquaculture hygiene management and aquaculture drugs by fish epidemic
prevention officers and others when using veterinary antibiotics for farm-raised aquatic animals.

Promote Infection Prevention and Control (IPC) of Food processing and Distribution Process

Embed Hazard Analysis and Critical Control Point (HACCP)RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Agriculture, Forestry and Fisheries (MAFF); Ministry of Health, Labour and Welfare (MHLW);
National Veterinary Assay Laboratory (NVAL); National Agriculture and Food Research Organization (NARO);
prefectural and municipal public health institutes; livestock hygiene service centers

EVALUATION INDICES


Number of veterinary vaccines, immunostimulants, and others put to practical use



Status of compliance with the biosecurity standards



Number of views on websites related to the Handbook for Hygienic Practice during Primary Production

Amount of vaccines used for livestock, farm-raised aquatic animals and pets

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 49

STRATEGY 3.3

STRENGTHEN THE OUTBREAK RESPONSECAPACITYAGAINST
ANTIMICROBIALRESISTANT INFECTIONSBACKGROUND

Recently, cases of nosocomial outbreak with Carbapenem-resistant Enterobacteriaceae (CRE) or other
antimicrobial-resistant organisms (AROs) are increasing. In the meanwhile, regarding the ability to implement
epidemiological studies and to take measures for infectious disease containment by a medical institution itself,
there are large differences in response capacity between medical institutions. In addition, as there aredifferences in knowledge and experience with antimicrobial-resistant infections (ARIs) among local
governments, it is necessary to strengthen the response capacity to outbreaks by antimicrobial-resistantinfections (ARIs) by establishing guidelines and providing training seminars.



Vancomycin-resistant enterococci (VRE) infections are a Category V infectious disease requiring notifiabledisease surveillance under the Act on the Prevention of Infectious Diseases and Medical Care for Patients with
Infectious Diseases, and the number of patients reported in the National Epidemiological Surveillance ofInfectious Disease has remained below 100 cases annually from 2011 to 2019. However, in 2020, there were
135 cases (as of January 25, 2021), exceeding the previous record of 120 cases in 2010. Overseas, a new
epidemic strain (pts-deficient Enterococcus faecium) was reported to have caused a large outbreak across statesin Oceania 74, and a large outbreak of this strain was subsequently reported in Europe. The large outbreakreported in Japan in 2018 in Aomori Prefecture was also caused by this epidemic strain.75Outbreaks of carbapenem-resistant Acinetobacter 76 and multidrug-resistant Mycobacterium tuberculosis(MDR-TB) 77 have also been reported overseas. Moreover, outbreaks of antimicrobial-resistant infections(ARIs) have mainly occurred within hospitals, but due to the recent spread of antimicrobial resistance (AMR)
in the community, there are growing concerns about the occurrence of community-acquired antimicrobialresistant infection (ARI) outbreaks. An outbreak of multidrug-resistant group A streptococcal infections wasreported in Israel in 2017.78 Since 2016, a large outbreak of ultra-multidrug-resistant typhoid infections has
been reported in Pakistan,79 and outbreaks of multidrug-resistant Salmonella spp. have been reported in China,
Taiwan, Israel, and elsewhere.80, 81, 82, 83 An outbreak of ultra-multidrug-resistant Shigella dysenteriae (XDR
Shigella sonnei) occurred in early 2022, mainly in Europe.84 Strengthening monitoring system and response
capacity to epidemic and outbreaks of antimicrobial-resistant organisms (AROs) in these food and waterborne

74

Carter GP, Buultjens AH, Ballard SA, et al. Emergence of endemic MLST non-typeable vancomycin-resistantEnterococcus faecium. J Antimicrob Chemother. 2016;71(12):3367-3371. doi:10.1093/jac/dkw314
75 Saito N, Kitazawa J, Horiuchi H, et al. Interhospital transmission of vancomycin-resistant Enterococcus faecium in Aomori,Japan. Antimicrob Resist Infect Control. 2022;11(1):99. Published 2022 Jul 23. doi:10.1186/s13756-022-01136-5
76 Rivera F, Reeme A, Graham MB, et al. Surveillance cultures following a regional outbreak of carbapenem-resistantAcinetobacter baumannii. Infect Control Hosp Epidemiol. 2022;43(4):454-460. doi:10.1017/ice.2021.162
77 Suppli CH, Norman A, Folkvardsen DB, et al. First outbreak of multidrug-resistant tuberculosis (MDR-TB) in Denmark
involving six Danish-born cases. Int J Infect Dis. 2022;117:258-263. doi:10.1016/j.ijid.2022.02.017
78 Ron M, Brosh-Nissimov T, Korenman Z, et al. Invasive Multidrug-Resistant emm93.0 Streptococcus pyogenes Strain
Harboring a Novel Genomic Island, Israel, 2017-2019. Emerg Infect Dis. 2022;28(1):118-126. doi:10.3201/eid2801.210733
79 Chatham-Stephens K, Medalla F, Hughes M, et al. Emergence of Extensively Drug-Resistant Salmonella Typhi Infections
Among Travelers to or from Pakistan - United States, 2016-2018. MMWR Morb Mortal Wkly Rep. 2019;68(1):11-13.
Published 2019 Jan 11. doi:10.15585/mmwr.mm6801a3
80 Merker M, Nikolaevskaya E, Kohl TA, et al. Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis
Beijing Clades, Ukraine, 2015. Emerg Infect Dis. 2020;26(3):481-490. doi:10.3201/eid2603.190525
81 Xiang Y, Li F, Dong N, et al. Investigation of a Salmonellosis Outbreak Caused by Multidrug Resistant Salmonella
Typhimurium in China. Front Microbiol. 2020;11:801. Published 2020 Apr 29. doi:10.3389/fmicb.2020.00801
82 Tiew WT, Janapatla RP, Chang YJ, et al. Emergence and spread in Taiwan of multidrug-resistant serotypes of
nontyphoidal Salmonella. Infection. 2022;50(2):475-482. doi:10.1007/s15010-021-01736-0
83 Cohen E, Kriger O, Amit S, Davidovich M, Rahav G, Gal-Mor O. The emergence of a multidrug resistant Salmonella
Muenchen in Israel is associated with horizontal acquisition of the epidemic pESI plasmid. Clin Microbiol Infect.
2022;28(11):1499.e7-1499.e14. doi:10.1016/j.cmi.2022.05.029
84 Extensively
drug-resistant Shigella sonnei infections - Europe - European Region (EURO). 2022
https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON364

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 50

infection diseases is also an important issue to be addressed.

A system that provides the necessary support for infection prevention and control (IPC), medical examinationof infectious diseases, and administrative responses needs to be developed, and the deployment of local
infectious disease specialists needs to be enhanced.

POLICIESDevelop manuals and guidelines to respond to both nosocomial and community outbreaks of antimicrobialresistant infections (ARIs) at a local level, and establish a system whereby local professionals provide support
to respond to an outbreak. Strengthen response capacities and a network through increasing education andtraining opportunities for those involved in the antimicrobial-resistant infection (ARI) outbreak control
measures

Establish a response system to a large-scale outbreak which causes a serious shortage of human resources by
dispatching experts throughout the country regarding epidemiological investigations, clinical management, andpublic health responses, as appropriate. In addition, the deployment of local infectious disease specialists will
be enhanced during normal times, and the response support system from the national level to the local level
will be strengthened.

ACTIONS

Support Local Responses to Outbreaks of Antimicrobial-Resistant Infections (ARIs)

Support local response to antimicrobial-resistant infection (ARI) outbreaks by the Regional Network for
Infectious Diseases Prevention and Control (tentative name) (see Strategy 3.1)
Update manuals and guidelines 85 to respond to nosocomial antimicrobial-resistant infections (ARIs)
outbreaks at a local levelEstablish a system at medical institutions during normal times and collaborate with health centers to
prepare for outbreaks by disseminating manuals and guidelines.

Discuss a mechanism for requesting assistance from hospitals to health centers, local infectious disease
specialists, prefectures, and the national government based on risk assessment in the manual andguidelines
Conduct training seminars for members of the "Regional Network for Infectious Diseases Prevention andControl (tentative name)" and the responsible persons in local governments (see Strategy 2.1)

Strengthen the Capacity to Respond to Large Scale Outbreaks
Enhance the talent pool of antimicrobial resistance (AMR) professionals86 who can respond in case of an
extreme shortage of human resources associated with an antimicrobial-resistant infection (ARI) outbreak

85 Manual for Infection Control in Nursing Homes, Guidance for responding to outbreaks of antimicrobial-resistant bacteria

in small and medium-sized hospitals, Responding to outbreaks of antimicrobial-resistant pathogens in health-care facilities:
guidance for the Western Pacific region (https://apps.who.int/iris/handle/10665/363498), Risk Assessment and Response
Guidelines for Carbapenem-Resistant Enterobacteriaceae (CRE) Infections by Health Centers - Toward Better
Collaboration Between Public Health Centers and Medical Institutions
86 Graduates of the Field Epidemiology Training Program Japan (FETP-J), antimicrobial-resistant infection (ARI)
professionals of the National Center for Global Health and Medicine and the National Institute of Infectious Diseases,
Infectious Disease Emergency Specialists (IDES) and antimicrobial-resistant infection (ARI) professionals in the fields ofpractical epidemiology, clinical management, infection prevention and control (IPC) and public health who belong to othermedical institutions and research institutes

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 51

RELATED MINISTRIES, AGENCIES, AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); NIID; National Center for Global Health and Medicine(NCGM); public health centers; and prefectural and municipal public health institutes

EVALUATION INDICES


Number of responses to the outbreak and the number of patients with antimicrobial-resistant infections(ARIs)



Number of training seminars implemented for relevant parties

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 52

GOAL 4PROMOTE APPROPRIATE USE OF
ANTIMICROBIALS IN THE FIELDS OFHEALTHCARE, LIVESTOCK AND AQUACULTURE

Strategies(4.1)

Promote Antimicrobial Stewardship at Medical Institutions(4.2)

Ensure Prudent Use of Antibiotics for Animals in the Fieldof Livestock and Aquaculture and Veterinary Medicine

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 53

STRATEGY 4.1

PROMOTE ANTIMICROBIAL STEWARDSHIP AT
MEDICAL INSTITUTIONSBACKGROUNDWhile infection prevention and control (IPC) at medical institutions contribute to the prevention of expansionof antimicrobial resistance (AMR), infection prevention and control (IPC) cannot prevent the emergence ofantimicrobial-resistant organisms (AROs) and the occurrence of antimicrobial-resistant infections (ARIs) byitself.

To minimize the occurrence of antimicrobial-resistant infections (ARIs) and to reduce the resultant disease
burden, it is extremely important to ensure antimicrobial stewardship (AMS) for inpatient and outpatient.87 In
Japan, the annual cost of inappropriate antibicotics prescribed for upper respiratory tract infection in 2016 wasestimated to be USD 297.1 million. 88

Antimicrobial stewardship (AMS) has effects to reduce unnecessary prescriptions and minimize the emergenceof antimicrobial-resistant organisms (AROs), while suppressing medical expenses. In Japan, there is a reportof an estimated cost saving of USD 150 thousand by reducing carbapenem-resistant bacteria through the efforts
of an in-house antimicrobial stewardship team (AST), 89 and another report showed a 25.8% reduction in
antibiotic treatment costs by providing intervention and feedback on dosing appropriateness, de-escalation, andrecommendations for blood culture collection by a team of physicians, pharmacists, and bacteriologists at a
local hospital.90

However, some medical institutions in Japan have promoted antimicrobial stewardship measures, including the
mandatory pre-authorization or reporting for specified antibiotics91 use. On the other hand, it is necessary toutilize the Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) as acomprehensive promotion system that integrates measures to promote antimicrobial stewardship (AMS).



In response to this situation, in the revision of medical fee in FY2018, the premium for support for appropriate
use of antibiotics, which is an evaluation of in-hospital antimicrobial stewardship team (AST), was newly
established as well as the premium for support for appropriate use of pediatric antibiotics in the pediatricoutpatient clinic fee and pediatric family practice fee to evaluate medical care that contributes to improving
patient and family understanding of appropriate use of antibiotics. The introduction of the premium for support
for appropriate use of pediatric antibiotics has resulted in a decrease of approximately 20% in the administrationof antibiotics to pediatric patients in outpatient clinics. In addition, with the revision of medical fee in FY2022,
the premium for support for appropriate use of pediatric antibiotics in otolaryngology was newly established,further promoting the appropriate use of antibiotics.









87 Society for Healthcare Epidemiology of America; Infectious Diseases Society of America; Pediatric Infectious Diseases

Society. Policy statement on antimicrobial stewardship by the Society for Healthcare Epidemiology of America (SHEA), theInfectious Diseases Society of America (IDSA), and the Pediatric Infectious Diseases Society (PIDS). Infect Control Hosp
Epidemiol. 2012;33(4):322-327. doi:10.1086/665010
88 Tsuzuki S, Kimura Y, Ishikane M, Kusama Y, Ohmagari N. Cost of inappropriate antimicrobial use for upper respiratory
infection in Japan. BMC Health Serv Res. 2020;20(1):153. Published 2020 Feb 28. doi:10.1186/s12913-020-5021-1
89 Akazawa T, Kusama Y, Fukuda H, et al. Eight-Year Experience of Antimicrobial Stewardship Program and the Trend of
Carbapenem Use at a Tertiary Acute-Care Hospital in Japan-The Impact of Postprescription Review and Feedback. Open
Forum Infect Dis. 2019;6(10):ofz389. Published 2019 Sep 5. doi:10.1093/ofid/ofz389
90 Fukuda T, Watanabe H, Ido S, Shiragami M. Contribution of antimicrobial stewardship programs to reduction of
antimicrobial therapy costs in community hospital with 429 Beds --before-after comparative two-year trial in Japan. J Pharm
Policy Pract. 2014;7(1):10. Published 2014 Aug 5. doi:10.1186/2052-3211-7-10
91 Broad-spectrum antibiotics including anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs and carbapenem
antibiotics

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 54Antimicrobial stewardship (AMS) is an area that essentially requires consideration concerning conflict ofinterest (COI) with the pharmaceutical companies. In Japan, following the formulation of the National Action
Plan on Antimicrobial Resistance (AMR), the Ministry of Health, Labour and Welfare issued the Manual of
Antimicrobial Stewardship, The1st Edition on June 1, 2017 and the Manual of Antimicrobial Stewardship, The
2nd Edition on December 5, 2019, while the Japanese Association for Infectious Diseases and the JapaneseSociety of Chemotherapy issued the "JAID/JSC Guide to Clinical Management of Infectious Diseases 2019,"
and the Japanese Society of Chemotherapy and the Japan Society for Surgical Infection issued the "Japanese
Clinical Practice Guidelines for antimicrobial prophylaxis in surgery"; there are various guidelines and otherpublications related to infectious disease care. On the other hand, it has been reported that the guidelines are
not always followed in the use of broad-spectrum antimicrobials in the clinical settings.92,93 

POLICIES

Based on the idea that conflict of interest (COI) between medical institutions/pharmacies and related companies,
etc. must be thoroughly managed when promoting antimicrobial stewardship (AMS), the "Antimicrobial
stewardship (AMS) Working Group" established under Ministry of Health, Labour and Welfare (MHLW) is to
update the Manual of Antimicrobial Stewardship as necessaryContinuously update and improve the Manual of Antimicrobial Stewardship based on the latest findings anddevelop guidance to enable each medical institution to formulate its antimicrobial stewardship (AMS)
guidelines and manuals for medical examination of infectious diseases based on antimicrobial susceptibility.
Promote antimicrobial stewardship (AMS) and appropriate medical examination of infectious diseases foroutpatients and inpatients through operation of antimicrobial stewardship teams (ASTs) to promoteantimicrobial stewardship (AMS) at medical institutions and the quality evaluation of antimicrobial stewardship(AMS)

Promote measures to enhance antimicrobial stewardship (AMS) concerning the prevention, diagnosis andtreatment of infectious diseases

ACTIONS

Publish guidelines/manuals for Antimicrobial StewardshipContinue to promote infection prevention and control (IPC) and antimicrobial stewardship (AMS) throughnecessary discussion at the "Antimicrobial Resistance (AMR) Subcommittee" and the "Antimicrobial
stewardship (AMS) Working Group" established within Ministry of Health, Labour and Welfare (MHLW).
(see Strategy 3.1)

Update the Manual of Antimicrobial Stewardship, enhance its content, and promote its use in clinicalpracticeExpand support for antimicrobial stewardship (AMS) for outpatients through the online monitoring system
for antimicrobial stewardship at clinics

Review regulations regarding diagnosis and treatment to promote Antimicrobial Stewardship(AMS)

Review information included in package inserts (e.g. Precautions for Use) for antimicrobials based on
scientific evidence

Reflect the findings based on the latest scientific evidence in Pharmacokinetics/Pharmacodynamics(PK/PD), etc. into the Manual of Antimicrobial Stewardship94 and other documents

92 Jung-ho Shin, Noriko Sasaki, Susumu Kunisawa, Yuichi Imanaka. Influence of criteria for nosocomial use of antimicrobial

agents on the selection of antimicrobial agents recommended in practice guidelines for patients with community-acquired
pneumonia, and the impact of its antimicrobial selection on outcomes. The 58th Annual Congress of Japan Society for
Healthcare Administration in Fukuoka and online, October 2-4, 2020 (Journal of the Japan Society for Healthcare
Administration Vol.57 Suppl. p.172)
93 2018 Ministry of Health, Labour and Welfare commissioned project: Evidence Based Medicine (EBM) Dissemination andPromotion Project “Medical Guideline Handbook” p3
94 First Edition (https://www.mhlw.go.jp/file/06-Seisakujouhou-10900000-Kenkoukyoku/0000166612.pdf),
Second Edition (https://www.mhlw.go.jp/content/10900000/000573655.pdf)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 55Conduct research on optimizing appropriate use initiatives in intravenous antibiotics



Based on related research results, review methods to further promote antimicrobial stewardship (AMS) for
outpatients95 (see Strategy 5.2)

Support establishment of a system to promote Antimicrobial Stewardship (AMS) at medical
institutions
Strengthen the specific antimicrobial stewardship (AMS) components in professional education andtraining for physicians, pharmacists, nurses, clinical technologists and particular professionals (seeStrategy 1.2)

Continue to support medical institutions in the formulation of management guidance of conflict of interest(COI)96 concerning antimicrobial stewardship (AMS), antimicrobial stewardship (AMS) guidelines, andmedical examination manuals for infectious diseases based on the institution-specific antimicrobial
susceptibility at each medical institution (see Strategy 2.4)



Establish antimicrobial stewardship teams (ASTs) at medical institutions and continue research on
securing dedicated employees, based on receipt information, etc.

Consider expanding to small and medium sized hospitals for the addition of antimicrobial stewardship(AMS) implementation based on the research resultsEstablish systems to dispatch experts, conduct education and to provide consultation services (see Strategy
1.2) through the Regional Network for Infectious Diseases Prevention and Control (tentative name) (seeStrategy 3.1), and promote infection control measures implemented through cooperation among medical
institutions based on the premium for improvement of infection control measuresConduct research on the development of the Antimicrobial Stewardship Support System (tentative name) 97
and the utilization of pharmacists (see Strategy 5.3)

RELATED MINISTRIES, AGENCIES AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); National Center for Global Health and Medicine (NCGM)EVALUATION INDICESThe number of medical institutions that implement a comprehensive antimicrobial stewardship (AMS)
programThe number of antimicrobial stewardship (AMS) support systems in each region

95 It has been demonstrated in the Cochrane Systematic Reviews that the prohibition of prescription of antibiotics to patientswith acute upper respiratory tract infection in their first visit has no association with prognosis, proving that this is one of themost substantiated antimicrobial stewardship (AMS) strategies. Spurling GK, Del Mar CB, Dooley L, Foxlee R, Farley R.
Delayed antibiotics for respiratory infections. Cochrane Database Syst Rev. 2013;(4):CD004417. Published 2013 Apr 30.
doi:10.1002/14651858.CD004417.pub4
Dar OA, Hasan R, Schlundt J, et al. Exploring the evidence base for national and regional policy interventions to combat
resistance. Lancet. 2016;387(10015):285-295. doi:10.1016/S0140-6736(15)00520-6.
96 Self-regulation of antimicrobial promotion activities by pharmaceutical companies and others at medical institutions,refrain from accepting research funding for research related to antimicrobial stewardship (AMS), etc.
97 Develop a system to ensure that the appropriate dose and frequency of antibiotics are administered and conduct researchon their effectiveness in antimicrobial stewardship and improving prognosis.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 56

STRATEGY 4.2

ENSURE PRUDENT USE OF ANTIBIOTICS FORANIMALS IN THE FIELD OF LIVESTOCK AND
AQUACULTURE AND VETERINARY MEDICINEBACKGROUND

Veterinary antibiotics and antibiotic feed additives used in livestock are important materials to protect the healthof livestock and to ensure the stable production of safe food. On the other hand, their use always involves a riskof selecting antimicrobial resistant bacteria that might bring adverse effects to human medicine, veterinary
medicine, and food safety.



Therefore, in Japan, based on the principles of risk analysis established by the international standards of theWorld Organisation for Animal Health (WOAH) and the Codex Alimentarius Commission, the Food Safety
Commission of Japan (FSC) conducts risk assessment concerning the impact of antimicrobial resistant bacteria
on human health through food. Based on the results, the Ministry of Agriculture, Forestry and Fisheries (MAFF)
formulates and implements risk management measures in accordance with the extent of risks.

Regarding veterinary antibiotic use, compliance with various regulatory systems under related laws andregulations98 is promoted through the monitoring and guidance by prefectural pharmaceutical inspectors, etc.,
thereby promoting appropriate use of veterinary antibiotics. In addition, guidelines for the prudent use ofveterinary antibiotics in the livestock industry have been established, and the government is working to promote
the prudent use of veterinary antibiotics by educating veterinarians and producers and providing guidance on
the use of veterinary antibiotics by prefectural governments.



In addition, the testing materials and criteria for antimicrobial susceptibility testing that veterinarians require
for the prudent use of veterinary antibiotics have been developed and enhanced.



Veterinary antibiotics for farm-raised aquatic animals are not currently included in the scope of the directionsor the prescription system for veterinary medicinal products that involves veterinarians. However, in eachprefecture, guidance for appropriate use of such antibiotics is provided by experts at fisheries research andlaboratory facilities and other organizations.



Appropriate use of antibiotic feed additives is ensured by specifying applicable feed products (targeted animal
species and breeding stages (products for lactation period, for fattening period, etc.)) and standard amounts tobe added in feed. 99 Products that may negatively affect human medicine are not to be designated as feed
additives.



Steady progress was made on the risk assessments concerning the impact of antimicrobial-resistant bacteria on
human health through food, and risk assessment was completed for all designated antibiotic feed additives.
Based on the experience of the risk assessment and international trends, the "Assessment Guideline for the
Effect of Food on Human Health regarding Antimicrobial-Resistant Bacteria Selected by Antimicrobial Use inFood Producing Animals" and "Ranking of the Importance of Antimicrobials against Bacteria which Affect
Human Health through Food Commodities" were revised in March 2022.



For pets, the "Working Group on the Prudent Use of Antimicrobials for Pets" has prepared a "Guidebook for
the Prudent Use of Antimicrobials for Pets" and is working to promote and educate clinical veterinarians forpets to ensure the prudent use.

98 To ensure the appropriate and limited use of veterinary antibiotics, measures are taken with regard to the use and salesof veterinary antibiotics through the requirement for examination by veterinarians (Veterinarians Act, Law No. 186 of 1949),
and the prohibition of sale to persons without prescriptions by veterinarians and the specification of standards for use (Acton Securing Quality, Efficacy and Safety of Products Including Pharmaceuticals and Medical Devices, Law No. 145 of 1960).
99 Measures are taken to promote the appropriate and limited use of antibiotic feed additives, based on the Act on Safety
Assurance and Quality Improvement of Feeds (Act No. 35 of 1953).

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 57

POLICIES


Continue to formulate risk management measures in accordance with the extents of risks and appropriately
implemented, based on the results of risk assessment concerning the impact of antimicrobial-resistant bacteria
on human health through food, conducted by Food Safety Commission of Japan (FSC), in accordance with theprinciples of risk analysis established by the international standards of the World Organisation for Animal
Health (WOAH) and the Codex Alimentarius Commission.



Establish and enhance methods required for ensuring the prudent use of veterinary antibiotics by veterinarians.



Examine and promote the expanded and strengthened involvement of experts in the use of veterinary antibiotics
for farm-raised aquatic animals.

ACTIONS

Promote risk assessment and risk management of the effects on human health via food of
antimicrobial resistance (AMR) due to use of antibiotics for animals
Formulate and appropriately implement risk management measures based on the guidelines for developing
risk management measures, taking into account the results of risk assessment conducted by Food Safety
Commission of Japan (FSC) (such measures may include the revocation of designation, temporary
prohibition of use, narrowed scope of applicable animal species and breeding stages, and strengthened
surveillance.)Adequately promote food safety risk assessment for antimicrobial-resistant bacteria; review, as needed,the "Assessment Guideline for the Effect of Food on Human Health regarding Antimicrobial-ResistantBacteria Selected by Antimicrobial Use in Food Producing Animals", which describes the methods andcriteria for the said food safety risk assessment, and the "Ranking of the Importance of Antimicrobials
against Bacteria which Affect Human Health through Food Commodities", which is ranking of importanceof antibiotics for humans to conduct risk assessment



Review, as needed, the guidelines for developing risk management measures concerning veterinary
antibiotics and antibiotic feed additives.

Establish a veterinary antimicrobial stewardship system
Grasp and analyze the total amount of human antibiotics and antibiotics for animals used in veterinary
medicine by "Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM)".



Implement calculation and international comparisons of the amount of antibiotics for animals per livestock
species based on appropriate use unit of antibiotics for animals



Establish a system to grasp the actual use of antimicrobials on each farm and utilize it for veterinarian's
medication guidance, etc.

Strengthen the system for ensuring the prudent use of antibiotics for animals
Among veterinarians and producers, ensure thorough implementation of prudent use in accordance withand gear up guidance as per "Basic Concepts concerning the Prudent Use of Antibiotics for Animals in
Livestock Production", "Guidance concerning the Appropriate Use of Aquaculture Drugs", and"Guidebook for the Prudent Use of Antimicrobials for Pets"; and improve contents of promotional andeducational tools targeted at veterinarians, producers, and pet owners (brochures, leaflets, etc) to promote
the prudent use of veterinary antibioticsCreate leaflets concerning the appropriate use of antibiotic feed additives, targeted at producers and feed
manufacturers.



Establish and strengthen test materials, determination methods and criteria and indices concerning theeffectiveness of treatment for antimicrobial susceptibility, as the basis for the prudent use of veterinary
antibiotics

Strengthen the leadership of experts (e.g. veterinarians, pharmaceutical inspectors, fish epidemic
prevention officers) in the use of veterinary antibiotics for farm-raised aquatic animals

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 58

RELATED MINISTRIES, AGENCIES AND INSTITUTIONSFood Safety Commission of Japan (FSC), Cabinet Office (CAO); Ministry of Agriculture, Forestry and Fisheries(MAFF); National Veterinary Assay Laboratory (NVAL); Food and Agricultural Materials Inspection Center(FAMIC); livestock hygiene service centers; fisheries research and laboratory facilities

EVALUATION INDICESThe number of risk management measures that are formulated and/or implemented

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 59

GOAL 5PROMOTE RESEARCH ON ANTIMICROBIALRESISTANCE AND FOSTER RESEARCH AND
DEVELOPMENT AND OTHER MEASURES TO
SECURE THE MEANS TO PREVENT, DIAGNOSE AND
TREAT THE ANTIMICROBIAL-RESISTANT
INFECTIONSStrategies(5.1)

Promote Research to Elucidate the Mechanism of theEmergence and Transmission of Antimicrobial Resistanceand its Socioeconomic Impact(5.2)

Promote Research on Public Awareness/Education on
Antimicrobial Resistance, Infection Prevention and Control,and Antimicrobial Stewardship(5.3)

Promote Clinical Research on the Optimization of Existing
Methods for Prevention, Diagnosis and Treatment of
Infectious Diseases(5.4)

Promote Research and Development of Novel Methods forPrevention, Diagnosis and Treatment and Promote theCooperation of Industry, Academia and Government(5.5)

Promote Global Research Collaboration on Antimicrobial
Resistance and Research and Development of Novel
Methods for Prevention, Diagnosis and Treatment of
Antimicrobial-resistant Infections(5.6)

Sustainable Research and Development of Antimicrobials
and Enhancement of Stable Supply
ClinicalBasic

Research on theemergence andtransmission of
antimicrobial
resistance

Research on surveillance
and risk assessment

Optimization of existing
methods for prevention,
diagnosis and treatment

Preclinical developmentof novel methods forprevention, diagnosis andtreatment

Clinical developmentof novel methods forprevention, diagnosis
and treatment

SocialResearch on
infection
prevention/
control andantimicrobial
stewardship

Evaluation of
impact on publicawareness,
education andsocioeconomics

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 60

STRATEGY 5.1

PROMOTE RESEARCH TO ELUCIDATE THE
MECHANISM OF THE EMERGENCE AND
TRANSMISSION OF ANTIMICROBIAL RESISTANCE
AND ITS SOCIOECONOMIC IMPACTBACKGROUND

To break the transmission chain of antimicrobial resistance (AMR), it is required to accurately elucidate theentire ecosystem of antimicrobial resistance (AMR), specifying the types of organisms that acquire
antimicrobial resistance (AMR), the mechanism of acquisition, and the channels and extent of the spread.
Activities have been enhanced globally to figure out this entire ecosystem of antimicrobial resistance (AMR).100



It is important to preserve strains isolated from antimicrobial-resistant organisms (AROs) and to accumulate
genome data including antimicrobial-resistant genes (ARGs) to promote antimicrobial resistance (AMR)related research and development (R&D), including the research on antimicrobial resistance (AMR)
mechanisms and the development of new methods for prevention, diagnosis and treatment. Identification of
epidemiological risk factors leading to the acquisition of antimicrobial resistance (AMR) and their linkage toantimicrobial resistance (AMR) mechanisms is also important to promote effective and implementable
antimicrobial resistance (AMR) measures. In Japan, the National Institute of Infectious Diseases establishedthe Japan Antimicrobial Resistant Bacteria Bank (JARBB) in 2019 and is building a cooperative system withoverseas partners to collect antimicrobial-resistant strains that are rare in Japan.



Estimation of the impact of antimicrobial resistance (AMR) on society and economy, including disease burden(e.g. mortality, incidence of complications, prolonged hospitalization) and economic burden (e.g. increased
medical expenses, opportunity costs) have been performed in the U.S., Europe and other regions, and based on
the data, the review committee on antimicrobial resistance (AMR) in United Kingdom (O'Neill Commission)
has estimated that deaths due to antimicrobial resistance (AMR) would reach 10 million worldwide by 2050,
and Gross Domestic Product of 1,000 trillion dollars would be lost if no measures will be taken in the future.101



According to the estimates made by Ministry of Health, Labour and Welfare (MHLW) study group using
Diagnosis Procedure Combination (DPC) data, hospitalization cost for a methicillin-resistant Staphylococcus
aureus (MRSA) infection was approximately 3.4 times higher than that for a non-methicillin-resistant
Staphylococcus aureus (MRSA) infection, hospitalization days approximately 3.0 times longer, and mortality
rate 3.7 times higher. Extrapolating these results to all 1,584 hospitals that had introduced the Per-Diem
Payment System based on Diagnosis Procedure Combination (DPC/PDPS) in 2014, the disease burden due tomethicillin-resistant Staphylococcus aureus (MRSA) infections was estimated to increase hospitalization costs
by 210 billion yen (3.41% of all impatient medical expenses), increase hospital stays by 4.34 million days
(3.02% of all hospitalization days), and increase deaths by 143,000 (3.62% of all deaths). 102 In addition, a study
conducted by the same group, with the cooperation of hospitals that have experienced outbreaks of
antimicrobial-resistant bacteria in the past, showed that economic losses due to outbreaks can be as high as 69.8
million yen in containment costs and 476 million yen in productivity losses, and that measures including early
information disclosure may limit these losses.103

100 D.G. Joakim Larsson & Carl-Fredrik FlachNature Reviews Microbiology 20, 257-269, 2022

（https://www.nature.com/articles/s41579-021-00649-x）
101 Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. The Review on Antimicrobial Resistance
Chaired by Jim O’Neill, December 2014.
102 Uematsu H, Yamashita K, Kunisawa S, Fushimi K, Imanaka Y. Estimating the disease burden of methicillin-resistant
Staphylococcus aureus in Japan: Retrospective database study of Japanese hospitals. PLoS One. 2017;12(6):e0179767.
Published 2017 Jun 27. doi:10.1371/journal.pone.0179767 Health and Labour Sciences Research Grants (Research on
Emerging and Re-emerging Infectious Diseases and Immunization) 2016, “Assessment of Risks in Health and Economics
Caused by Epidemic of Antimicrobial Resistant Organisms”.
103 Morii D, Tomono K, Imanaka Y. Economic impact of antimicrobial-resistant bacteria outbreaks on Japanese hospitals.
Am J Infect Control. 2020;48(10):1195-1199. doi:10.1016/j.ajic.2019.12.006 Health, Labour and Welfare Policy Research
Grants (Research on Emerging and Re-emerging Infectious Diseases and Immunization) 2019, “Research on
Implementation of National Action Plan on Antimicrobial Resistance (AMR)”

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 61

POLICIES

Promote research to elucidate the emergence and transmission of antimicrobial resistance (AMR) based on the
genome analysisPromote antimicrobial resistance (AMR) genome surveillance to figure out mechanisms of the emergence andtransmission of antimicrobial resistance (AMR) and drug discovery by promoting the preservation of
antimicrobial-resistant organism (ARO) strains, and utilizing the pathogen genomics database that contains
Japan Antimicrobial Resistant Bacterial Bank (JARBB) and antimicrobial resistance (AMR) provided by the
National Institute of Infectious Diseases (NIID).



In the fields of agriculture and aquaculture, utilize the genome database of antimicrobial resistant bacteria (JVEG) developed by the National Veterinary Assay Laboratory (NVAL), to contribute to antimicrobial
resistance (AMR) measures in collaboration with the antimicrobial resistance (AMR) genome database(GenEpid-J) of the National Institute of Infectious Diseases (NIID) and Japan Antimicrobial Resistant Bacterial
Bank (JARBB).



Conduct research on estimating the impact of Antimicrobial-resistant Infections (ARIs) on health, society andeconomy and publish the results in plain language to raise awareness.



ACTIONS

Promote research on the emergence and transmission of antimicrobial resistancePromote research to elucidate the mechanisms of emergence and transmission of antimicrobial resistance(AMR) , the transmission process of antimicrobial-resistant organisms (AROs)/ antimicrobial resistancegenes (ARGs), and the ecosystem of antimicrobial-resistant organisms (AROs)/ antimicrobial resistancegenes (ARGs) including their spread and interaction in general society and the environment (see Strategy
2.1)



Promote preservation of isolates in JARBB available to industry, academia, and medicine (see Strategy
2.4 and Strategy 5.4)

Promote surveillance on pathogen trends using Japan Antimicrobial Resistant Bacterial Bank (JARBB)104;
elucidate the mechanisms of emergence and transmission of antimicrobial resistance (AMR); promote
R&D including drug discovery, etc.; and collect genomic information on isolates in Japan and overseas(Japan Antimicrobial Resistant Bacterial Surveillance (JARBS))

Promote research on one-health antimicrobial resistance (AMR) surveillance using E. coli (tricycle
surveillance)105 in collaboration with the World Health Organization (WHO)Promote research to establish and utilize a system to collectively manage strains and clinical informationof antimicrobial-resistant organisms (AROs)



Promote research on the relevance of the process of antimicrobial resistance (AMR) transmission between
humans and animals utilizing the genome database (J-VEG)Conduct research to elucidate the mechanisms of emergence and transmission of antimicrobial resistance(AMR), and Critical Control Points (CCP) in livestock and aquaculture, and veterinary medicine

Conduct research on the environmental impact of antimicrobials and antimicrobial-resistant organisms(AROs) in sewage

Promote research on the health and socioeconomic burdens of antimicrobial resistancePromote research on the disease burden 106 and economic burden of antimicrobial-resistant infections(ARIs) at healthcare institutions107 (see Strategy 2.1)

104 Antimicrobial resistance (AMR) genome database included
105

Surveillance targeting E. coli producing extended-spectrum beta-lactamases (ESBLs) in humans, animals, andenvironment based on a multidisciplinary integrated surveillance protocol developed by the World Health Organization(WHO)
106 Incidence rate, mortality, rate of sequelae, hospitalization days, disease burden indices (e.g. Disability-adjusted life years(DALYs), Years lived with disability (YLD)), etc.
107 Research is in progress under Health and Labour Sciences Research Grants 2015, “Assessment of Risks in Health andEconomics Caused by Epidemic of Antimicrobial Resistant Organisms”.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 62Promote research concerning the effect of antimicrobial resistance (AMR) measures on the reduction of
medical expenses



Promote research on systematic risk assessment based on surveillance resultsSupport utilization of Diagnosis Procedure Combination (DPC) and the National Database for Prescription
and National Health Check-up (NDB)

RELATED MINISTRIES, AGENCIES AND INSTITUTIONSNational Healthcare Policy Secretariat, Cabinet Office; Ministry of Education, Culture, Sports, Science andTechnology (MEXT); Ministry of Health, Labour and Welfare (MHLW); Ministry of Agriculture, Forestry and
Fisheries (MAFF); Ministry of the Environment; NIID; NVAL; National Agriculture and Food Research
Organization (NARO); Food and Agricultural Materials Inspection Center (FAMIC); National Center for Global
Health and Medicine (NCGM); Japan Agency for Medical Research and Development (AMED)EVALUATION INDICESThe number of papers funded by national grants in the relevant areasThe number of genomes accumulated in the genome database

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 63

STRATEGY 5.2

PROMOTERESEARCH
ON
PUBLIC
AWARENESS/EDUCATION ON ANTIMICROBIALRESISTANCE, INFECTION PREVENTION AND
CONTROL, AND ANTIMICROBIAL STEWARDSHIPBACKGROUND

To implement policies for combating antimicrobial resistance (AMR), it is important not only to accumulate
existing scientific evidence and incorporate it into public health measures, but also to create new scientificevidence in Japan, and share it with society and the international community.For effective public awareness and education, research on identifying people’s knowledge, attitudes andpractices concerning antimicrobial use and antimicrobial resistance (AMR), and messages leading to behavior
modification is crucial. At home and overseas, research has been undertaken regarding effective campaign
methods targeted at people and at healthcare professionals.108,109



Regional cooperation in infection prevention and control (IPC) is one of the areas where Japan is leading, andresearch is in progress concerning its effectiveness.110

With respect to antimicrobial stewardship (AMS), the total amount of antimicrobial use is relatively small inJapan; however, the proportion of broad-spectrum third-generation oral cephalosporins, fluoroquinolones, andmacrolides is high. In addition, according to a survey conducted in 2018 by the Health and Labour Sciences
Research Group, while many hospitals have a working infection control team (ICT), the content of its activities
varies from hospital to hospital, with only about 70% of hospitals having standards for the number of days or
antimicrobial agents administered, and only 60% and 50% having standards for the use of anti-methicillinresistant Staphylococcus aureus (MRSA) drugs and wide-spectrum antibiotics, respectively.111



In the fields of livestock and aquaculture, surveillance and research have been conducted to find indices andscientific evidence required for the appropriate and prudent use of veterinary antibiotics.For the effective implementation of antimicrobial resistance (AMR)-related measures, it is required to specify
process indicators to identify progress in measures, as well as outcome indices to evaluate effectiveness. It isalso necessary to examine the validity of such indices. The Health and Labour Sciences Research Group
conducted an international comparison of measures in their study. 112 In the UK, which has experienced
significant reductions in the number of bloodstream infections caused by methicillin-resistant Staphylococcus
aureus (MRSA) in the past, a number of systematic policy interventions were implemented to combat
healthcare-associated infections (HAIs), combining outcome-based incentives and interventions based on thenumber of healthcare-associated infections (HAIs), and interventions by multidisciplinary hospital infection
control teams (ICT). On the other hand, Japan uses voluntary surveillance and focuses on recommendations
and persuasive interventions, thus presenting different interventions/appropriate combinations for future
consideration.

108 Gu Y, Fujitomo Y, Soeda H, et al. A nationwide questionnaire survey of clinic doctors on antimicrobial stewardship inJapan. J Infect Chemother. 2020;26(2):149-156. doi:10.1016/j.jiac.2019.12.005
109 Kamata K, Tokuda Y, Gu Y, Ohmagari N, Yanagihara K. Public knowledge and perception about antimicrobials andantimicrobial resistance in Japan: A national questionnaire survey in 2017. PLoS One. 2018;13(11):e0207017. Published2018 Nov 5. doi:10.1371/journal.pone.0207017
110 Research is in progress under Health and Labour Sciences Research Grants (Grants-in-aid for Scientific Research)
2014, “Research concerning Infection Control at Medical Institutions” and under Health and Labour Sciences Research
Grants 2013, “Establishment of a Surveillance System for Nationwide Trends in the Use of Antibiotics, and Evaluation of
Infection Prevention Premiums”.
111 Shin JH, Mizuno S, Okuno T, et al. Nationwide multicenter questionnaire surveys on countermeasures against
antimicrobial resistance and infections in hospitals. BMC Infect Dis. 2021;21(1):234. Published 2021 Feb 27.
doi:10.1186/s12879-021-05921-2 Health, Labour and Welfare Policy Research Grants (Research on Emerging and Reemerging Infectious Diseases and Immunization) 2019, “Research on Implementation of National Action Plan on
Antimicrobial Resistance (AMR)”
112 Mizuno S, Iwami M, Kunisawa S, et al. Comparison of national strategies to reduce meticillin-resistant Staphylococcus
aureus infections in Japan and England. J Hosp Infect. 2018;100(3):280-298. doi:10.1016/j.jhin.2018.06.026 Health,Labour and Welfare Policy Research Grants (Research on Emerging and Re-emerging Infectious Diseases and
Immunization) 2018, “Research on Implementation of National Action Plan on Antimicrobial Resistance (AMR)”

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 64

POLICIES

Conduct research on effective intervention methods and benchmarking methods to measure the effectivenessto promote public awareness and education, infection prevention and control (IPC), and antimicrobial
stewardship (AMS)

ACTIONS

Research on behavior changePromote surveys on people’s knowledge, attitudes and practices to identify, evaluate and improve theeffects of activities aimed at public awareness-raising and education

Promote clinical and epidemiologic research concerning antimicrobial stewardship (AMS) andinfection prevention and control (IPC) in human medicine
Promote research to evaluate progress in antimicrobial stewardship (AMS) and its effectiveness and costeffectiveness at medical institutions (see Strategy 4.1)

Promote clinical research on the utilization of basic microbiological tests that contributes to antimicrobial
stewardship (AMS) (see Strategy 2.4)



Review research on the effectiveness of antibiotic prescription regulation for outpatients with acute upper
respiratory tract infection (see Strategy 4.1)



Review research on the risk of colonization by antimicrobial-resistant organisms (AROs) and the relevant
screening methods at medical institutions



Review research on the detection status of antimicrobial-resistant bacteria and antimicrobial use at nursing
care facilities (see Strategy 3.1)

Conduct research to examine the way in which local experts and local governments in outbreak areas
should be involved in each healthcare institution in order to effectively prevent healthcare-associatedinfection (HAI) outbreak cases or prevent their spread, and to study the effectiveness of such involvement(see Strategy 3.3)

Conduct research to evaluate the appropriateness of existing evaluation indicators (disinfectant use andcompliance rates) for hand hygiene and to develop evaluation indicators for stratification (each medical
institution/region/country)Conduct research toward the development of a comprehensive regional collaboration system to provide
benchmarking data on infection prevention and control (IPC) and antimicrobial stewardship (AMS), andsurveillance information to the Regional Network for Infectious Diseases Prevention and Control(tentative name) (see Strategy 3.1)

Conduct research and development (R&D) for assisting tools to support appropriate diagnosis andtreatment of infectious diseases in line with antimicrobial stewardship (AMS) policies

Conduct research on the isolation rate and molecular epidemiology of antimicrobial resistance (AMR) in
home healthcare113

Conduct research on antimicrobial use (AMU) with pharmacies as a starting point114

Conduct research on methods for understanding the actual status of antimicrobial-resistant H. pylori

113 Researchon the transmission of antimicrobial-resistant organisms (AROs) among patients under home care is inprogress under Health and Labour Sciences Research Grants (Grants-in-aid for Scientific Research) 2015, regional medical
platform development and promotion project “Isolation Trend and Molecular Epidemiology of Multidrug-resistant Organisms
in Patients under Home Care”.
114 Conduct research on the actual status of antibiotic use and information on the status of unused prescription medicines.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 65Research on antimicrobial stewardship (AMS) of antibiotics for animals and infection
prevention and control (IPC) in livestock and aquaculture, and veterinary medicine
Promote research for rearing management that does not rely on antimicrobial agents by livestock species,
considering changes in the antimicrobial resistance rates following the discontinuation of use of antibiotics
for animals, and secondary risks

Conduct research to develop rapid and accurate diagnostic methods to ensure appropriate use of antibiotics
for animals

RELATED MINISTRIES, AGENCIES AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); Ministry of Agriculture, Forestry and Fisheries (MAFF);
National Institute of Infectious Diseases (NIID); National Veterinary Assay Laboratory (NVAL); National
Agriculture and Food Research Organization (NARO); Food and Agricultural Materials Inspection Center(FAMIC); National Center for Global Health and Medicine (NCGM)EVALUATION INDICESProgress in research related to the actions described above

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 66

STRATEGY 5.3

PROMOTE CLINICAL RESEARCH ON THE
OPTIMIZATION OF EXISTING METHODS FORPREVENTION, DIAGNOSIS AND TREATMENT OF
INFECTIOUS DISEASESBACKGROUNDThe issues of drug lag have been discussed due to limited availability of new vaccines, diagnostics and drugs
in Japan, which are available overseas.In response to these issues with respect to infectious diseases, the Evaluation Committee on Unapproved or
Off-labeled Drugs with High Medical Needs has made requests for development to pharmaceutical companies,
which have led to the authorization of benzylpenicillin benzathine in 2021, which is used as a first-line drug
for syphilis worldwide and has no reported antimicrobial-resistant bacteria in syphilis, in addition to intravenous
metronidazole, colistin and other drugs.115 There are also challenges with the supply of injectable cephazolin
by some manufacturers and distributors, and measures are needed to maintain a stable supply of antimicrobials.

On the other hand, among antimicrobials that are useful against antimicrobial-resistant organisms (AROs) andare used in Japan but not available overseas due to discontinuation of sales or other reasons, there are agentsthat are not recommended in international guidelines due to insufficient clinical evidence.116For some antimicrobials, administration and dosage have not been adjusted based on the latest
Pharmacokinetics/Pharmacodynamics (PK/PD) to enable appropriate antimicrobial use. There are also drugs
that include indications covered by health insurance, which are not globally recommended for specificinfectious diseases. For example, guidelines in the U.S. and Europe don’t recommend to use third-generation
oral cephalosporin antibiotics for patients with streptococcal pharyngitis.117,118

Japan's antimicrobial use (AMU) is not high compared to other developed countries. In the AWaRe
classification 119 recommended by World Health Organization (WHO), an indicator for antimicrobial
stewardship (AMS), World Health Organization (WHO) aims for the ratio of "Access" antibiotics to all
antibiotics to be at least 60%. In Japan, however, the percentage tends to be lower than in other countries, andwas 21.1% in 2020.120 Clinical and epidemiologic research toward the optimization of existing methods forprevention, diagnosis and treatment should be promoted to further promote appropriate use.

115 List of drugs for which companies were invited, or for which requests for development were made, based on the resultsof evaluation at the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs, Ministry of Health,Labour and Welfare (MHLW): http://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/iyakuhin/kaihatsuyousei/;
Accessed on 7July 2022.
116 Nafcillin, ertapenem, nitrofurantoin, cefiderocol, etc.
117 Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A
streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America [published correction appears in Clin
Infect Dis. 2014 May;58(10):1496. Dosage error in article text]. Clin Infect Dis. 2012;55(10):e86-e102.
doi:10.1093/cid/cis629
118 ESCMID Sore Throat Guideline Group, Pelucchi C, Grigoryan L, et al. Guideline for the management of acute sorethroat. Clin Microbiol Infect. 2012;18 Suppl 1:1-28. doi:10.1111/j.1469-0691.2012.03766.x
119 The AWaRe classification is based on the World Health Organization's (WHO) Model Lists of Essential Medicines, 20thedition, as an indicator of appropriate use of antibiotics. It classifies antibiotics into four categories: "Access" (Antibiotics
that should be of high quality, affordable, and widely available in all countries, with low concern for antimicrobial resistance,
used as first or second-line drugs for common infections, e.g., ampicillin, cephalexin, etc.), "Watch" (Antibiotics that should
only be used for limited diseases or indications due to concerns about antimicrobial resistance, e.g., vancomycin,
meropenem, levofloxacin, ceftriaxone, etc.), "Reserve" (Antibiotics that should be used as a last resort when other measures
are no longer available, e.g., tigecycline, colistin, daptomycin, etc.), and Unclassified. This classification was revised in2019 and the new category "non-recommended" (antibiotics that are not recommended for clinical use by the World HealthOrganization (WHO), e.g., cefoperazone/sulbactam) was added.
120 Muraki Y, Kitamura M, Maeda Y, et al. Nationwide surveillance of antimicrobial consumption and resistance toPseudomonas aeruginosa isolates at 203 Japanese hospitals in 2010. Infection. 2013;41(2):415-423. doi:10.1007/s15010013-0440-0

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 67

POLICIES

Implement reviews on existing methods of prevention, diagnosis and treatment of infectious diseases which areavailable overseas and contribute to containment of antimicrobial resistance (AMR), and promote research on
optimizing the indications and usage of antimicrobials to be used in Japan, based on the latest scientific evidencePromote research to accumulate the scientific evidence and apply them to antimicrobial resistance (AMR)
control measures

ACTIONS

Research on the optimization of existing methods for prevention, diagnosis and treatment
Conduct research to introduce or re-introduce useful methods for prevention, diagnosis and treatment of
infectious diseases for antimicrobial resistance (AMR) control measures, which are available in othercountries but not in Japan (either unapproved or withdrawn from the market)

Promote research on usage regulation to preserve the effectiveness of antimicrobials, which is usefulmeasures for antimicrobial resistance (AMR)

Conduct research on the treatment of antimicrobial-resistant infections (ARIs) by modification oftherapeutics including combination therapy and high-dose therapy

Conduct research on the development of the Antimicrobial Stewardship System (tentative name) and theutilization of pharmacists (same as Strategy 4.1)

Implement research on the evaluation of Japan based on the AWaRe classification recommended by theWorld Health Organization (WHO) as an indicator of antimicrobial stewardship (AMS) and research on
actions in antimicrobial stewardship team (AST) and outpatient prescriptions using the AWaRe
classification

RELATED MINISTRIES, AGENCIES AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); National Institute of Infectious Diseases (NIID); National
Center for Global Health and Medicine (NCGM)EVALUATION INDICESProgress in research related to the actions described above

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 68

STRATEGY 5.4

PROMOTE RESEARCH AND DEVELOPMENT OFNOVEL METHODS FOR PREVENTION, DIAGNOSISAND
TREATMENT AND PROMOTE THE
COOPERATION OF INDUSTRY, ACADEMIA AND
GOVERNMENTBACKGROUND
Japan has developed many antimicrobials which are used as standard drugs globally. Drugs developed in Japan
include meropenem and doripenem, which are carbapenem antibiotics that have been used as the last resort
against antimicrobial-resistant organisms (AROs), colistin, one of the few antibiotics that are effective on
carbapenem-resistant Enterobacteriaceae (CRE), and delamanid, an anti-tuberculous agent that is effective on
multidrug-resistant tuberculosis.



Since 2016, 13 new antimicrobials have been launched in Japan, including 7 antibiotics , 121 2 antifungal
agents, 122 2 antiparasitic agents 123 , 1 antituberculosis agents, 124 and 1 anti non-tuberculous mycobacterium
agents125. Of these, lascufloxacin, fosravuconazole, and ceftolozane in ceftolozane/tazobactam were originatedin Japan. Although it is necessary to further promote the development of new antibiotics, the development of new
antimicrobials is subject to antimicrobial stewardship (AMS) regulation to prevent further antimicrobial
resistance (AMR), which undermines economic incentives for drug discovery at pharmaceutical companies.



As detective method, the SMA disc method for detecting metallo-β-lactamase-producing bacteria and the PCRbased ORF Typing (POT) method for molecular epidemiological analysis by polymerase chain reaction (PCR)
have been developed in Japan, but they are still few in number.

In Japan, research and development (R&D) on infectious diseases has been specifically promoted under theJapan Agency for Medical Research and Development (AMED), which was established in April 2015 as per
the Act on Promotion of Healthcare Policy (Act No. 48 of May 2014) and the Act on the Independent
Administrative Agency of Japan Agency for Medical Research and Development (Act No. 49 of 2014). In
Africa and Asia, tuberculosis control is still one of the most important policy issues due to the increase ofmultidrug-resistant Mycobacterium tuberculosis (MDR-TB) caused by inadequate tuberculosis treatment andother factors. Under these circumstances, Japan is actively working on the development of drugs for developing
countries against malaria, tuberculosis and neglected tropical diseases (NTDs), etc., by utilizing the Global
Health Technology Fund (GHIT Fund), which also contributes to the promotion of international cooperation in
health and medical care.

In the field of livestock production, surveillance and research are implemented by universities and privateorganizations under national projects, concerning determination methods for antimicrobial susceptibility
required for the prudent use of veterinary antibiotics.

121 Lascufloxacin, a new quinolone; relebactam/imipenem/cilastatin, a combination of carbapenem and beta-lactamase

inhibitor; ceftolozane/tazobactam, a combination of cephalosporin and beta-lactamase inhibitor; tedizolid, an anti methicillinresistant Staphylococcus aureus ( MRSA) drug; fidaxomicin, an anti-clostridium difficile infection (CDI) drug; bezlotoxumab(Monoclonal antibody), which inhibits recurrent clostridium difficile infection (CDI); and benzylpenicillin benzathine, a longacting drug used to treat syphilis.
122 Fosravuconazole, a novel triazole for the treatment of tinea unguium; Posaconazole, a novel azole for the treatment of
deep mycosis
123 Artemether/lumefantrine, an antimalarial drug; spiramycin, an anti-toxoplasma drug
124 Bedaquiline for treatment of multidrug-resistant tuberculosis
125 Inhaled amikacin for non-tuberculous mycobacterium infection

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 69

POLICIES

Promote research to contribute to the development of novel methods for prevention, diagnosis and treatment
against human and veterinarian infectious diseases, including the development of new vaccines and otherinfection disease preventive methods, rapid diagnostics that contributes to the promotion of antimicrobial
stewardship (AMS), antimicrobials with novel mechanisms, and other non-traditional therapeutics



Enhance the measures taken by the council to promote public private partnership on antimicrobial resistance(AMR) to set R&D priorities and create incentives for R&D, taking into account the frequency of emergenceof antimicrobial-resistant organisms(AROs) and needs to obtain medical countermeasures in the shortest period
possible

ACTIONS

Promote research and development of novel methods for prevention
Promote the R&D of new vaccines to reduce incidence of zoonosis

Promote R&D on novel preventive approaches that do not induce the emergence of antimicrobial-resistantorganisms (AROs)126

Promote research and development of novel diagnostics
Promote R&D on rapid and simplified diagnostic tools (including POC) and equipment 127 for
identification of causal organisms and antimicrobial resistance (AMR), which contribute to antimicrobial
stewardship (AMS) and antimicrobial-resistant organisms (AROs) containment measuresDevelop simplified test methods that contribute to the prudent use of veterinary antibiotics on production
sites

Promote research and development of novel therapeutics


Further promote R&D of antimicrobials with novel mechanisms that contributes to the treatment of humanantimicrobial-resistant infections (ARIs) (see Strategy 5.6)

Promote R&D of non-conventional therapeutics128 for infectious diseases that differ from antimicrobials

Promote cooperation among industry, academia and governmentStrengthen the measures by the 7 Academic Society and the Drug Discovery Promotion Review
Committee and the AMED Public and Private Partnerships for Infectious Diseases R&D, and promote
drug discovery in the infectious disease field through industry-academia-government collaboration, aimed
at the R&D of methods for prevention, diagnosis and treatment of antimicrobial-resistant infections (ARIs),
and at promoting research and other activities to elucidate mechanisms of emergence and transmission of
antimicrobial resistance (AMR)

Create incentives for research and development
Promote harmonization of clinical evaluation methods for the development of antimicrobials amonginternational regulatory authorities, including Japan, the U.S., and the EU (see Strategy 5.5 and Strategy
6.1)



Promote R&D for methods for prevention, diagnosis and treatment of antimicrobial-resistant tuberculosis,
malaria, etc. through Global Health Innovation Technology (GHIT) Fund

Continue the mechanism for the priority review of drugs for antimicrobial-resistant infections (ARIs) inregulatory approval process (see Strategy 5.6)

126 E.g. preventive approach in specific clinical conditions, such as the prevention of human infectious diseases related tosurgery or chemotherapy
127 E.g. expedited antimicrobial susceptibility testing, multiplex nucleic acid amplification tests for antimicrobial-resistancegenes (ARGs), immune chromatography for antimicrobial resistance gene (ARG) products
128 E.g. phage therapy, immunotherapy including antibodies, synthesized microbial flora (e.g. synthesized intestinalbacterial flora that simulates the normal intestinal bacterial flora, which is expected as a therapy for Clostridium difficile
infection), gene therapy

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 70Continue consultation service for pharmaceutical strategies specialized in drugs for antimicrobial-resistantinfections (ARIs) in regulatory approval processSupport for the development of vaccines, immunostimulants, which contribute to reduce the use of
antimicrobials

Introduce a market incentive mechanism for new antimicrobials under the "Antimicrobial Securement
Support Program" (see Strategy 5.6)

RELATED MINISTRIES, AGENCIES AND INSTITUTIONS
Office for Healthcare Policy, Cabinet Office (CAO); Ministry of Foreign Affairs (MOFA); Ministry of Education,
Culture, Sports, Science and Technology (MEXT); Ministry of Health, Labour and Welfare (MHLW); Ministryof Agriculture, Forestry and Fisheries (MAFF); National Institute of Infectious Diseases (NIID); National
Veterinary Assay Laboratory (NVAL); National Agriculture and Food Research Organization (NARO), National
Center for Global Health and Medicine (NCGM); Japan Agency for Medical Research and Development(AMED)EVALUATION INDICESProgress in research related to the actions described above

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 71

STRATEGY 5.5

PROMOTE GLOBAL RESEARCH COLLABORATIONON AMR AND RESEARCH AND DEVELOPMENT OFNOVEL METHODS FOR PREVENTION, DIAGNOSISAND
TREATMENTOF
ANTIMICROBIALRESISTANT INFECTIONSBACKGROUND

Research on antimicrobials as countermeasure to combat against antimicrobial resistance (AMR), antimicrobial
resistance (AMR) diagnostic techniques and vaccines to reduce humans and animals that become infected, havebeen stagnated for many years. Recently, the U.S. and Europe have re-accelerated research and development(R&D) concerning novel methods for prevention, diagnosis and treatment. The "Group of Seven (G7) Finance
Ministers’ Statement on Actions to Support Antibiotic Development" agreed at the 2021 Group of Seven (G7)
Finance Ministers' Meeting commits to take specific and appropriate additional measures to enhance antibiotic
research and development with respect to antimicrobial resistance (AMR) and to create appropriate economic
conditions to bring new drugs to market. 129 The 2022 Group of Seven (G7) Leaders' Statement also called forenhanced research and innovation in new anti-microbials in international partnerships. As is represented by the U.S. Generating Antibiotics Incentives Now (GAIN) Act, R&D of new antimicrobials
is in progress around the world. Harmonized R&D activities under international joint research initiatives 130 are
important to avoid overlapping or uncoordinated competition.



The U.S. and Europe have promoted cooperation for new drug development through the Transatlantic Task
Force on Antimicrobial Resistance (TATFAR) since 2009, 131 and the Joint Programming Initiative on
Antimicrobial Resistance (JPIAMR) and the Global Research Collaboration for Infectious Diseases
Preparedness (GloPID-R) are promoting international collaboration in antimicrobial resistance (AMR) research.
In 2015, Japan Agency for Medical Research and Development (AMED) joined the Joint Programming
Initiative on Antimicrobial Resistance (JPIAMR) and the Global Research Collaboration for Infectious
Diseases Preparedness (GloPID-R),132 ,133 and is working to promote international collaboration.

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for
Human Use (ICH) has established common guidelines for Good Clinical Practice (GCP) concerning
pharmaceuticals for human use, including antimicrobials. 134 The use of common clinical evaluation
requirements in the clinical development process has been desired to promote R&D on a global scale and to
expedite the commercialization of the products. As a result of technical discussions between the regulatory
authorities in Japan, the U.S., and the EU, no agreement was finally reached on the standardization of theguidelines themselves, taking into account the local characteristics of infectious diseases. Since the outbreak ofcoronavirus infectious disease, emerged in 2019 (COVID-19), each country has been working to promotecollaboration and regulatory harmonization among international regulatory authorities, not only in clinicalevaluation methods for antimicrobials, but also in response to infectious disease in general. Regarding documents required for application for approval of veterinary medicinal products, such as antibiotic
agents, including antimicrobial resistance (AMR)-related documents, the International Cooperation on
Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) has
established common tripartite guidelines in Japan, U.S., and the EU.135 ,136

129 Group of Seven (G7) Finance Ministers’ Statement on Actions to Support Antibiotic Development
130 Joint

Programming Initiative on Antimicrobial Resistance (JPIAMR); Global Research Collaboration for Infectious
Disease Preparedness (GloPID-R)
131 Transatlantic
Task Force on Antimicrobial Resistance, Centers for Disease Prevention and Control,
http://www.cdc.gov/drugresistance/tatfar/, accessed on 24 December 2015.
132 JPIAMR Press Release, Japan joins as newest JPIAMR member, 19 October 2015. http://www.jpiamr.eu/japan-joinsas-newest-jpiamr-member/,accessed on 24 December 2015.
133 GloPID-R Press Release, New member joins the fight against global epidemics, 4 August 2015. http://www.glopidr.org/new-member-joins-the-fight-against-global-epidemics/, acceded on December 24, 2015.
134 Guidelines for Good Clinical Practice E6 (R1), ICH harmonized tripartite guideline – Implemented in June 1996.
135 Pre-approval information for registration of new veterinary medicinal products for food producing animals with respect
to antimicrobial resistance, VICH GL27 (Antimicrobial resistance: pre-approval) - Implemented in December 2004.
136 Studies to evaluate the safety of residues of veterinary drugs in human food: General approach to establish a
microbiological ADI, VICH GL36 (R) (Safety) May 2004 – Implemented in June 2013

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 72

POLICIES


Contribute to promote R&D on a global scale through contribution to the international research collaboration
through participating in the international activities related to antimicrobial resistance (AMR) by AMED andother related institutions and exchanging informationWork with regulatory authorities in Japan, U.S., the EU and other countries to accelerate the development of
new drugs, including harmonization of clinical evaluation methods to promote the development of
antimicrobials in cooperation on a global scale

ACTIONS

Promote international harmonization of clinical evaluation methods
Promote harmonization of clinical evaluation methods for development of antimicrobials amonginternational regulatory authorities, including Japan, the U.S., and the EU (see Strategy 5.4 and Strategy
6.1)



Promote harmonization of documents required for application for approval of veterinary medicinal
products, such as antibiotic agents, in the framework of the International Cooperation on Harmonisationof Technical Requirements for Registration of Veterinary Medicinal Products (VICH) including Japan, theU.S. and the EU (see Strategy 6.1)

Promote international research collaboration
Continue participation in international activities related to antimicrobial resistance (AMR), includinginternational personnel exchanges of researchers, and utilize the Japan-led ARO Alliance for ASEAN andEast Asia (ARISE) platform to contribute to the promotion of research and development related toantimicrobial resistance (AMR)137



Establish a system of collaboration with overseas Public Private Partnership (PPP) scheme, bringpromising seeds related to antimicrobial resistance (AMR) to the early clinical stage, and bank therapeutic
drug candidates ,to accelerate drug development in the event of outbreaks caused by pathogenic bacteria,
etc.,



Promote bridging between research and policies through international dialogue, including cooperation
with foreign national funding organizations such as the U.S. National Institutes of Health (NIH) and the

U.K. Medical Research Council (MRC) (see Strategy 6.1)
Promote four R&D areas 1) surveillance system and laboratory network, 2) health-care management, 3)
antimicrobial access and regulation, and 4) research and development, on Asia-Pacific One Health
Initiative on AMR (ASPIRE) with Asian countries

RELATED MINISTRIES, AGENCIES AND INSTITUTIONS
Office for Healthcare Policy, Cabinet Office (CAO); Ministry of Foreign Affairs (MOFA); Ministry of Education,
Culture, Sports, Science and Technology (MEXT); Ministry of Health, Labour and Welfare (MHLW); Ministryof Agriculture, Forestry and Fisheries (MAFF); National Institute of Infectious Diseases (NIID); National
Veterinary Assay Laboratory (NVAL); Pharmaceuticals and Medical Devices Agency (PMDA); National Center
for Global Health and Medicine (NCGM); Japan Agency for Medical Research and Development (AMED)

137 Research Project on Clinical Research and Clinical Trial Promotion, Enhancement of the involvement of International

ARO Alliance with Asian and Japanese academic institutions and establishment of a network of cooperation with relevantorganizations to respond to infectious disease emergencies. Haruhito SUGIYAMA, Hospital Director, Center Hospital of the
National Center for Global Health and Medicine

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 73

EVALUATION INDICESCreation of joint documents among international regulatory authorities including Japan, the U.S., and the
EU that outlines regulatory measures that contribute to the development of antimicrobials



Creation of internationally harmonized guidelines on the studies required for application for the approvalof veterinary pharmaceuticals, such as antibiotic agents

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 74

STRATEGY 5.6

SUSTAINABLE RESEARCH AND DEVELOPMENT OF
ANTIMICROBIALS AND ENHANCEMENT OFSTABLE SUPPLYBACKGROUND
Japan has developed many antimicrobials which are used as standard drugs globally. Drugs developed in Japan
include meropenem and doripenem, which are carbapenem antibiotics that have been used as the last resort
against antimicrobial-resistant organisms (AROs), colistin, one of the few antibiotics that are effective on
carbapenem-resistant Enterobacteriaceae (CRE), and delamanid, an anti-tuberculous agent that is effective on
multidrug-resistant tuberculosis.

Research on antimicrobials, a weapon in the combat against antimicrobial resistance (AMR), has been stagnant
for many years, and in recent years, international efforts have been made to re-accelerate research anddevelopment on novel methods for prevention, diagnosis and treatment.

In 2020, the "AMR Action Fund" was established to launch four new antimicrobials by 2030, funded by morethan 20 pharmaceutical companies worldwide, with support and backing from outside the pharmaceuticalindustry, including the World Health Organization (WHO) and the European Investment Bank. 138In the research project for the development promotion of novel antimicrobials for emerging and re-emerging
infectious diseases, epidemiological surveys, basic research and development of basic technologies on
antimicrobial-resistant bacteria are promoted to strengthen measures against infectious diseases, while
promoting integrated research and development of drugs, including diagnostic drugs, therapeutic drugs andvaccines. In addition, research and development of antimicrobial agents are also supported in the Cyclic
Innovation for Clinical Empowerment (CiCLE).

For the continuous development of new antimicrobials, it is important to create an attractive investment
environment and build an environment in which new antimicrobials are continuously launched, in addition to
public research fund support for R&D (so-called "push incentives"), and market incentives (so-called "pullincentives")139 are required to motivate companies to pursue R&D by increasing the predictability of profits
after launch. The international community also discussed antimicrobial incentives at the Group of Seven (G7)
Finance Ministers' Meeting in 2021, including consideration of a wide range of options with particularemphasis on supporting relevant market incentives, and the Group of Seven (G7) Leaders' Statement in 2022
also called for the encouragement of the development of new antimicrobials with particular emphasis on market
incentives. Market incentives are being introduced or considered in the United States, 140 United Kingdom,141
Sweden,142 and other countries. In the Group of Seven (G7) process, the Group of Seven (G7) countries are
expected to promote research and development of new antibiotics and international cooperation, and to play aleading role in international actions.

In addition, supply shortages of antibiotics are occurring around the world, and Japan is also experiencing largescale supply shortages of antibiotic, including challenges with the supply of injectable cephazolin in 2019.
Stable supply of antibiotics is an important issue to promote antimicrobial stewardship (AMS) and to control
further spread of antimicrobial resistance (AMR), and measures to maintain stable supply of antimicrobials are
required in addition to promote research and development of new antibiotics.

138 AMR Action Fund https://www.amractionfund.com/ja/ ,accessed on 4 July 2022.
139 In contrast to push incentives, which are incentives directly related to R&D, such as research support subsidies and tax

benefits for R&D expenditures, pull incentives are incentives that motivate the promotion of R&D, such as preferential postmarket drug prices, pre-screening of drug prices, guaranteed purchase of new drugs, market entry incentives, preferential
exclusivity period and permission for transfer of exclusivity period to other products.
140 The U.S. Generating Antibiotic Incentives Now Act (GAIN Act) includes the priority review process for new antimicrobial
candidates, patent term extension, etc. In June 2021, the PASTEUR Act was resubmitted in Congress as a bill.
141 Mark Perkins, David Glover, “Mark Perkins and David Glover Medicine,” https://www.england.nhs.uk/blog/how-the-nhsmodel-to-tackle-antimicrobial-resistance-amr-can-set-a-global-standard/,accessed on 4 July 2022.
142
PublicHealthAgencyof
Sweden,“Availabilityofantibiotics,”
1
December
2020,
https://www.folkhalsomyndigheten.se/the-public-health-agency-of-sweden/communicable-disease-control/antibiotics-andantimicrobial-resistance/availability-of-antibiotics/,accessed on 4 July 2022.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 75

POLICIES

Explore concrete methodologies to secure therapeutic drugs for antimicrobial-resistant bacteria, such as market
incentives, and introduce themPromote maintenance of a stable supply of antimicrobials

ACTIONS

Promote research and development of new antimicrobials
Promote R&D of antimicrobials with novel mechanisms that contribute to the treatment of humanantimicrobial-resistant infections (ARIs) (see Strategy 5.4)

Pilot introduction of a market incentive mechanism in the antimicrobial market
Introduce a market incentive mechanism for new antimicrobials under the "Antimicrobial Securement
Support Program" (see Strategy 5.4)

Continue the mechanism for the priority review system of drugs for antimicrobial-resistant infections(ARIs) in regulatory approval process (see Strategy 5.4)

Strengthen stable supply of antimicrobials by promoting domestic production of raw materials,
etc.
Implement "Pharmaceutical Stable Supply Support Program" to strengthen the supply chain of
antimicrobials and other pharmaceuticals that are highly dependent on overseas suppliers of active
pharmaceutical ingredients, etc., and to develop a stable supply system in Japan

RELATED MINISTRIES, AGENCIES AND INSTITUTIONSMinistry of Health, Labour and Welfare (MHLW); Pharmaceuticals and Medical Devices Agency (PMDA);
National Center for Global Health and Medicine (NCGM); Japan Agency for Medical Research and Development(AMED)EVALUATION INDICESThe number of new antimicrobials developed, and the number of those approved

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 76

GOAL 6ENHANCE GLOBAL MULTIDISCIPLINARY
COUNTERMEASURES AGAINST ANTIMICROBIALRESISTANCE

Strategies(6.1)

Strengthen Japan’s Leadership for Global Policies on
Antimicrobial Resistance(6.2)

Promote International Cooperation to Achieve the Global
Action Plan on Antimicrobial Resistance

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 77

STRATEGY 6.1

STRENGTHEN JAPAN’S LEADERSHIP FOR
GLOBALPOLICIESON
ANTIMICROBIALRESISTANCEBACKGROUND
 Antimicrobial resistance (AMR) is considered as a global health security threat and has been discussed at theWorld Health Organization (WHO) and the Group of Seven (G7) process. It remains one of the most important
health issues.143
 In Japan, antimicrobial resistance (AMR) control measures have been promoted in the fields of medicine,
livestock and aquaculture for many years, and antimicrobial resistance (AMR) surveillance systems have been
established. Antimicrobial use has also been at a lower level than the average of Organisation for Economic
Co-operation and Development (OECD). 144 Thus, Japan should play a leading role in AMR control measuresin the world, particularly in the Asia-Pacific region. The "Asia-Pacific One Health Initiative on AMR(ASPIRE)" was established in 2016 to promote the One Health approach in Asia-Pacific countries.
 Japan should also make international contribution as a Leading Country of Antimicrobial Resistance (AMR)
Action Package of the Global Health Security Agenda (GHSA), a multilateral initiative aimed at strengthening
the implementation of World Health Organization’s (WHO) International Health Regulation (IHR), for the
purpose of enhancing capacities on infectious diseases in each country. The AMR Clinical Reference Center(AMRCRC) and the Antimicrobial Resistance (AMR) Research Center are both designated as World HealthOrganization (WHO) collaborating centers and conduct international activities for antimicrobial stewardship(AMS) and countermeasures against antimicrobial resistance (AMR).
 In the fields of livestock and aquaculture, the Ministry of Agriculture, Forestry and Fisheries (MAFF) has madecontribution by participating in related meetings and proactively providing inputs in the process of formulatinginternational standards of the World Organisation for Animal Health (WOAH), the Code of Practice andGuidelines of the Codex Alimentarius Commission, and Food and Agricultural Organization of the United
Nations.
 In the ongoing initiative by the World Organisation for Animal Health (WOAH) to establish a database ofantibiotics for animals, Japanese experts have participated in the relevant meetings to provide data and advice.
 In the environmental area, antimicrobial resistance (AMR) was identified as one of the six areas of concern in
the United Nations Environment Programme’s Frontiers Report released at the third session of the United
Nations Environment Assembly, and the United Nations Environment Programme (UNEP), in cooperation with
the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO),
and the World Organisation for Animal Health (WOAH), has been working on a "Quadripartite"145 initiative.
Japan closely monitors the United Nations Environment Programme’s (UNEP) activities.


POLICIES
 Support global antimicrobial resistance (AMR) control measures by World Health Organization (WHO) both ata high level and at a grass root level, particularly in the Asia-Pacific region, and take actions to support
implementation of the Global Action Plan on Antimicrobial Resistance (AMR) through the Antimicrobial
Resistance (AMR) Action Package of the Global Health Security Agenda (GHSA)
 Promote research, development, and international cooperation and play a leading role in international actions
with the aim of strengthening commitment to antimicrobial resistance (AMR) in the Group of Seven (G7)
process, including the 2023 Group of Seven (G7) Hiroshima Summit, the Group of Seven (G7) Nagasaki Health
Ministers' Meeting, and the Group of Seven (G7) Miyazaki Agriculture Ministers' Meeting.
143 Abe S. Japan's vision for a peaceful and healthier world. Lancet. 2015;386(10011):2367-2369. doi:10.1016/S0140-

6736(15)01172-1
144 Muraki Y, Kitamura M, Maeda Y, et al. Nationwide surveillance of antimicrobial consumption and resistance toPseudomonas aeruginosa isolates at 203 Japanese hospitals in 2010. Infection. 2013;41(2):415-423. doi:10.1007/s15010013-0440-0
145 Partnership between the following four organizations: World Health Organization(WHO), Food and Agriculture
Organization (FAO), World Organisation for Animal Health (WOAH) and United Nations Environment Programme (UNEP)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 78 Support to strengthen international initiatives on antimicrobial resistance (AMR), including the formulation andrevision of international standards and the establishment of a database by the World Organisation for Animal
Health (WOAH), and contribute to international measures related to antimicrobial resistance (AMR) under the
Codex Alimentarius Commission, by participating in the process for revising the relevant standards

ACTIONS

Promote global policies on antimicrobial resistance (AMR)Support efforts of World Health Organization (WHO) against antimicrobial resistance (AMR)


Share information among stakeholders in Asian countries and international organizations, promoteantimicrobial resistance (AMR) control measures in each country by holding the annual Tokyo AMR
One-Health Conference continuously
Further promote efforts in antimicrobial resistance (AMR) measures in Group of Seven (G7) processIn the Group of Seven (G7) process, and promote research and development that contributes tocombating antimicrobial resistance (AMR), and play a leading role in international actions including
strengthening efforts related to antimicrobial resistance (AMR) and the introduction of new market
incentives for the development of antimicrobials
Support efforts against antimicrobial resistance (AMR) by FAO and World Organisation for Animal Health(WOAH) Continue to support efforts to create and revise the FAO guideline and international standards of theWorld Organisation for Animal Health (WOAH) on antimicrobial resistance (AMR), and to create a
database for monitoring the use of antibiotics for animals
Contribute to efforts of the Codex Alimentarius Commission on antimicrobial resistance (AMR) Contribute by participating in the efforts to revise the Code of Practice and Guidelines of the Codex
Alimentarius Commission on antimicrobial resistance (AMR)

Promote efforts as a Leading Country of the Antimicrobial Resistance (AMR) Action Package of Global
Health Security Agenda (GHSA) Promote international cooperation through multilateral dialogue, including cooperation with foreign
national funding organizations such as the U.S. National Institutes of Health (NIH) and the U.K. Medical
Research Council (MRC) (see Strategy 5.5) Promote harmonization of clinical evaluation methods for the development of anti-microbial agents amonginternational regulatory authorities, including Japan, the U.S., and the EU. (see Strategy 5.5)

Contribute through participation in the work to develop and revise the global common study guidelines
required for the approval of veterinary antibiotics in the framework of the International Cooperation on
Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH),
including Japan, the U.S., and the EU (see Strategy 5.5)



Contribute to the efforts to combat antimicrobial resistance (AMR) by monitoring closely the moves of
the United Nations Environment Programme (UNEP)RELATED MINISTRIES, AGENCIES AND INSTITUTIONS
Office for COVID-19 and Other Emerging Infectious Disease Control, Cabinet Secretariat; National Healthcare
Policy Secretariat, Cabinet Office; Ministry of Foreign Affairs (MOFA); Ministry of Agriculture, Forestry and
Fisheries (MAFF); Ministry of the Environment; National Institute of Infectious Diseases (NIID); National
Veterinary Assay Laboratory (NVAL); Pharmaceuticals and Medical Devices Agency (PMDA); Food andAgricultural Materials Inspection Center (FAMIC); National Center for Global Health and Medicine (NCGM);
Japan Agency for Medical Research and Development (AMED)

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 79

EVALUATION INDICESProgress in each action

Countries participating in the relevant meetingsGroup of Seven (G7) Progress Report, Commitment 13 (AMR) Indicators

Progress in the attainment of the Global Health Security Agenda (GHSA) Antimicrobial Resistance(AMR) Action Package targets

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 80

STRATEGY 6.2

PROMOTE INTERNATIONAL COOPERATION TO
ACHIEVE THE GLOBAL ACTION PLAN ON
ANTIMICROBIAL RESISTANCEBACKGROUND
 The Global Action Plan on Antimicrobial Resistance (AMR) by the World Health Organization (WHO) calls
for donor countries to support to achieve the Global Action Plan, particularly with regard to surveillance,
ensuring the availability of antimicrobials with measures to ensure their efficacy, and new methods forprevention, diagnosis and treatment.146
 At the 2016 Tokyo Meeting of Health Ministers on Antimicrobial Resistance in Asia, the Asia-Pacific One
Health Initiative on AMR (ASPIRE) was adopted to collaboratively confront the issue of antimicrobial
resistance (AMR) in the Asia-Pacific region and draw a roadmap to achieve regional antimicrobial resistance(AMR) control measures. Asia-Pacific One Health Initiative on AMR (ASPIRE) identified four priority areas:
1) surveillance system and laboratory network, 2) health-care management, 3) antimicrobial access andregulation, and 4) research and development. This was followed by the Kobe Communiqué of the Group of
Seven (G7) Health Ministers and the Political Declaration on Antimicrobial Resistance (AMR) at the HighLevel Meeting of the 71st session of the United Nations General Assembly. In response to these developments,
the Tokyo Antimicrobial Resistance (AMR) One Health Conference was held in 2017, where the promotion of
the Global Action Plan to combat antimicrobial resistance (AMR) in Asia was discussed and a summary of theresults was presented. The 2019 Tokyo Antimicrobial Resistance (AMR) One Health Conference was cohosted by the Ministry of Health, Labour and Welfare (MHLW) and the World Health Organization Western
Pacific Regional Office (WPRO), and the Asia-Pacific One Health Initiative on AMR (ASPIRE) Coordinating
Committee was formed to advance the four priority issues (pillars). At the 2021 Tokyo Antimicrobial
Resistance (AMR) One Health Conference, led by the chair, the current status of the four priority issues (pillars)
and future activities were discussed under the Asia-Pacific One Health Initiative on AMR (ASPIRE)
Coordinating Committee.  2021 World Health Organization (WHO) accredited the National Center for Global Health and Medicine AMR
Clinical Reference Center (AMRCRC) as a "World Health Organization (WHO) Collaborating Center for
prevention, preparedness and response to Antimicrobial Resistance" and the Antimicrobial Resistance ResearchCenter at the National Institute of Infectious Diseases as a "World Health Organization (WHO) Collaborating
Center for Antimicrobial Resistance (AMR) surveillance and research".
 Japan has a long history of R&D on antimicrobials and control of infectious diseases, as well as a history ofpromoting pharmaceutical quality control, high-quality surveillance, and clinical infection prevention andcontrol (IPC). Through Japan International Cooperation Agency (JICA), Japan has undertaken cooperation in
infection prevention and control (IPC) and the capacity building with a particular focus on countermeasuresagainst healthcare-associated infections (HAIs). From these viewpoints, Japan is able to provide support for
antimicrobial resistance (AMR) measures in a broad range.
 Japan has also undertaken international cooperation concerning antimicrobial resistance (AMR) in theframework of the Research on Emerging and Re-emerging Infectious Diseases and Immunization handled by
the Ministry of Health, Labour and Welfare (MHLW).
 In the fields of livestock and aquaculture, Japan has cooperated in training held by the World Organisation for
Animal Health (WOAH) and Food and Agricultural Organization of the United Nations (FAO), and dispatchedexperts in antimicrobial-resistant organisms to seminars requested by individual countries, among othercooperative efforts.

POLICIES
 Promote international cooperation in antimicrobial resistance (AMR) with a focus on the Asia-Pacific region,
through further collaboration among related agencies and institutions, research institutes, business enterprises
and other entities

146 Global Action Plan on Antimicrobial Resistance, World Health Organization 2015, ISBN 978 92 4 150976 3.

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ACTIONSInternational cooperation in public healthPromote international cooperation for AMR measures in the Japan Agency for Medical Research andDevelopment (AMED) and the National Institute of Infectious Diseases (NIID) by:

Strengthening the surveillance function by utilizing a Japan’s online surveillance platform147

Implementing the capacity-building of laboratories for AMR examinations, coupled with thestrengthening surveillance

Developing new pharmaceutical seeds for prevention, diagnosis and treatment through AMR genome
databaseContributing to surveillance activities for antimicrobial-resistant (AMR) Mycobacterium leprae in the
Asia-Pacific region
Promote the efforts of the Antimicrobial Resistance (AMR) Research Center at the National Institute of
Infectious Diseases and the National Center for Global Health and Medicine (NCGM) AMR Clinical
Reference Center (AMRCRC) as a World Health Organization (WHO) Collaborating Center Supporting the World Health Organization (WHO) actions in the Western Pacific region by raisingawareness of antimicrobial stewardship (AST), infection prevention, surveillance, and antimicrobial
resistance (AMR) in each country, as well as responding to outbreaks of antimicrobial-resistantorganisms (AROs)
 Strengthen implementation of the following measures in the Western Pacific regionStrengthen the AMR surveillance in each country by utilizing WHONET148 and the overseas version ofthe "Japan Nosocomial Infections Surveillance (JANIS)" (ASIARS-Net)



Enhance capacity for testing for antimicrobial-resistant organisms (AROs)



Technical assistance for countries participating in the One Health Antimicrobial Resistance (AMR)
Surveillance (tricycle surveillance) using E. coli in collaboration with the World Health Organization(WHO)

Support pathogen analysis of antimicrobial resistance (AMR) outbreaks by utilizing Whole genome
sequencing (WGS)



Develop guidance document for Antimicrobial resistance (AMR) surveillance and outbreak response

Support for revision of the Global AMR Surveillance System (GLASS)



Promote infection prevention and control (IPC) activities, promote access to antimicrobials and theirappropriate use to preserve their effectiveness, and enhance laboratory functions through the JICA
technical cooperation

Promote international cooperation for elimination of antimicrobial resistant tuberculosis utilizing new
methods for diagnosis and treatment for antimicrobial resistant tuberculosis developed in Japan andapproved by World Health Organization (WHO)

International cooperation in animal health

Support the promotion of international cooperation by international organisations such as Food andAgricultural Organisation (FAO) and the World Organisation for Animal Health (WOAH) concerning
AMR control measures, particularly in the Asian region
147 E.g.

Japan Nosocomial Infections Surveillance (JANIS), Japanese Veterinary Antimicrobial Resistance Monitoring
System (JVARM), antimicrobial resistance (AMR) genome database (GenEpid-J)
148 Microbiology laboratory database software that was developed by World Health Organization (WHO) Collaborating
Center for Antimicrobial Resistance Surveillance in Brigham and Women's Hospital, Boston, U.S., and has been used in
130 countries worldwide

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 82

In collaboration with the World Organisation for Animal Health (WOAH), promote international
cooperation concerning surveillance and monitoring, utilizing the World Organisation for Animal Health(WOAH) collaborating center function in the National Veterinary Assay Laboratory (NVAL), as well as
the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary
Medicinal Products (VICH) Outreach Forum

RELATED MINISTRIES, AGENCIES AND INSTITUTIONSNational Healthcare Policy Secretariat, Cabinet Office; Ministry of Foreign Affairs (MOFA); Ministry of Health,Labour and Welfare (MHLW); Ministry of Agriculture, Forestry and Fisheries (MAFF); NIID; NVAL; JICA;
National Agriculture and Food Research Organization (NARO); National Center for Global Health and Medicine(NCGM); AMEDEVALUATION INDICESThe number of seminars held and the number of participating countries

The number of countries with which Japan has cooperated in the development and implementation ofnational action plans on antimicrobial resistance (AMR)

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OUTCOME INDICES FOR THE ACTION PLAN
The following outcome indices are specified for National Action Plan on AMR (2023-2027).

HUMAN-RELATED INDICES
1.

Maintain the number149 of patients with vancomycin-resistant Enterococci (VRE) infections in 2027 at 80 orless (the level as of 2019)2.

Lower the methicillin resistance150 of Staphylococcus aureus to 20% or less by 2027

3.

Maintain the fluoroquinolone resistance 151 of E. coli at 30% or less in 2027.

4.

Lower the carbapenem (MEPM=R) resistance 152 of Pseudomonas aeruginosa to 3% or less by 2027.

5.

Maintain a carbapenem resistance 153 of E. coli and Klebsiella pneumoniae at 0.2% or less in 2027

* The antimicrobial resistance rate projection chart is based on Japan Nosocomial Infections Surveillance (JANIS) datafrom 2011 to 2021, and the numbers of future detections were predicted by Poisson regression for antimicrobial-susceptible
and resistant bacteria, respectively, based on the data of target bacteria detected in the samples (blood, urine, andrespiratory tract) for the antimicrobial-resistant bacteria subject to this outcome measure. The antimicrobial resistance rates
were calculated using the total number of bacteria detected in each year as the denominator and the number ofantimicrobial-resistant bacteria as the numerator. The impact of seasonality, antimicrobial consumption, and Corona virus
infectious disease, emerged in 2019 (COVID-19) from 2011 were included as variables in the projection, and the figures
were calculated up to 2027. Note that the results should be considered as reference values with uncertainty, since theprojection is for a long period of time, from 2022 to 2027. The antimicrobial resistance rates were calculated individuallyfrom published Japan Nosocomial Infections Surveillance (JANIS) data quarterly.
149 Vancomycin-resistant Enterococci infections are one of the most serious antimicrobial resistance threats, currently
expanding worldwide due to the paucity of therapeutic options available. It is a antimicrobial resistant organism for whichhorizontal transmission in hospitals and elderly care facilities should be controlled, and the actual number of infections is a
new additional indicator of infection control during normal times (notifiable disease surveillance). It can spread acrosshospitals and within a community and can also serve as an indicator for evaluating local infection control collaboration. The
goal is to prevent the spread of the disease in the community and maintain the current low number of infections
150 The methicillin resistance rate of Staphylococcus aureus is about 50% in 2020, which is high compared to otherdeveloped countries. Since bloodstream infections contribute significantly to the disease burden and with the intention of
excluding the effects of bacterial carriage, blood specimens shall be used as indicators. Based on data from 2011 to 2021,
the estimated rate in 2027 is 32%, considering the impact of seasonality, antimicrobial consumption, and Corona virus
infectious disease, emerged in 2019 (COVID-19) and the measured rate of 35.9% in 2020. The target is set at 20%,
considering that the promotion of infection prevention and control (IPC) to be implemented in this national action plan will
accelerate the rate by 1.4% annually.
151 The fluoroquinolone resistance rate of E. coli is highly correlated with fluoroquinolone usage. Since it is more difficult totreat than non-resistant bacteria and accounts for a large proportion of deaths in Japan, we will continue to use it as anindicator. The indicator is based on urinary specimens, as it targets urinary tract infections in the outpatient setting, in which
antimicrobial-resistant bacteria are directly linked to the treatment. Based on data from 2011 to 2021, the estimated rate
in 2027 is 42%, considering the impact of seasonality, antimicrobial consumption, and Corona virus infectious disease,
emerged in 2019 (COVID-19), and the measured rate of 35.0% in 2020. The target is set at 30%, considering that thepromotion of antimicrobial stewardship (AMS) and thorough infection prevention and control (IPC) for urinary catheter
infections to be implemented in this national action plan will accelerate the rate by 2.4% annually.
152 The carbapenem resistance rate of Pseudomonas aeruginosa is 11.0% as of 2020, a figure that is not high as comparedto other countries. Bloodstream infections are used as an index using blood samples with the intention of excluding theeffects of bloodstream infections that contribute significantly to the disease burden and the effects of bacterial carriage.
Based on data from 2011 to 2021, the estimated rate in 2027 is 6%, considering the impact of seasonality, antimicrobial
consumption, and Corona virus infectious disease, emerged in 2019 (COVID-19), and the measured rate of 7.1% in 2020.
The target is set at 3%, considering that the promotion of infection prevention and control (IPC) to be implemented in thisnational action plan will accelerate the rate by 0.6% annually.
153 Carbapenem-resistant Enterobacteriaceae (CRE) infections are a growing and serious antimicrobial resistance threat
worldwide due to the paucity of therapeutic options. Fortunately, the carbapenem resistance rates of Escherichia coli andKlebsiella pneumoniae in Japan are extremely low at 0.1% and 0.2%, respectively, as of 2020. Therefore, appropriate
antimicrobial resistance measures should be taken to maintain the antimicrobial resistance rates at the same level.

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6.

Reduce antimicrobial use154 per day per 1,000 inhabitants by 15% from 2020 levels by 2027

7.

Reduce the use155 of oral third generation cephalosporins, oral fluoroquinolones, and oral macrolides per day
per 1,000 inhabitants by 40%, 30%, and 25%, respectively, from 2020 levels by 2027.

8.

Reduce the use156 of intravenous carbapenems per day per 1,000 inhabitants by 20% from 2020 levels by 2027.

Supplemental Antimicrobial use targets will improve patient outcomes through appropriate antimicrobial use andminimize the impact of antimicrobial resistance by reducing unnecessary antimicrobial use.

* The antimicrobial use projection chart calculates daily use per 1,000 population based on National Database for
Prescription and National Health Check-up (NDB) data from 2013 to 2019 and used Poisson regression to project future
antimicrobial use. Only the impact of the National Action Plan on Antimicrobial Resistance (AMR) (2016-2020) was enteredas a variable when forecasting, and figures were calculated up to 2027. Since this is a long-term forecast from 2021 to
2027, the results should be considered as a reference value with uncertainty.
154 The daily antimicrobial use in Japan in 2020 is estimated to be 10.4 per 1,000 people, which is relatively low comparedto Europe (Figure 1). The daily antimicrobial use per 1,000 population is 13.1 DID in 2019 and 10.4 DID in 2020.Based ondata from 2013 to 2019 and considering the impact of the National Action Plan on Antimicrobial Resistance (AMR) (20162020), the projected value for 2027 is 9.0 DID. The target is set at a 15% decrease (8.85 DID), considering that thepromotion of antimicrobial stewardship (AMS) for upper respiratory tract infection in this National Action Plan will further
accelerate the rate by 0.3% annually starting in 2020.
155 The daily use of oral third-generation cephalosporins per 1,000 population is 2.72 DID in 2019 and 1.93 DID in 2020.
The projected value for 2027 is 1.24 DID based on data from 2013 to 2019, considering the impact of the National Action
Plan on Antimicrobial Resistance (AMR) (2016-2020). The target is set at 40% reduction (1.16 DID) considering that thepromotion of antimicrobial stewardship (AMS) for upper respiratory tract infection in this National Action Plan will further
accelerate the rate by 0.8% annually starting in 2020.
The daily use of oral fluoroquinolones per 1,000 population is 2.46 DID in 2019 and 1.76 DID in 2020. The projected value
for 2027 is 1.32 DID based on data from 2013 to 2019 and considering the impact of implementation of the National Action
Plan on Antimicrobial Resistance (AMR) (2016-2020). The target is set at 30% reduction (1.23 DID), considering that thepromotion of antimicrobial stewardship (AMS) for upper respiratory tract infection in this National Action Plan will accelerate
the rate by 1% annually from 2020.
The daily use of oral macrolides per 1,000 population is 4.37 DID in 2019 and 3.30 DID in 2020. The projected value for2027 is 2.49 DID based on data from 2013 to 2019, considering the impact of implementation of the National Action Plan
on Antimicrobial Resistance (AMR) (2016-2020). The target is set at 2.48 DID (25% reduction), considering that thepromotion of antimicrobial stewardship (AMS) for upper respiratory tract infection in this National Action Plan will further
accelerate the rate by 0.1% annually starting in 2020.
156 The daily use of intravenous carbapenem antibiotics per 1,000 population is 0.063 DID in 2019 and 0.058 DID in 2020.
The projected value for 2027 is 0.05 DID based on data from 2013 to 2019, considering the impact of implementation of
the National Action Plan on Antimicrobial Resistance (AMR) (2016-2020). The target is set at 20% reduction (0.046 DID),
considering that the promotion of antimicrobial stewardship (AMS) for upper respiratory tract infection in this National Action
Plan will further accelerate the rate by 1.5% annually starting in 2020.

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ANIMAL-RELATED INDICES
1.

Lower the tetracycline resistance157 of E. coli to 20% or less in cattle, 50% or less in swine, and 45% or less inchickens by 2027

2.

Lower the third-generation cephalosporin resistance 158 of E. coli to 1% or less in cattle, 1% or less in swine,
and 5% or less in chickens by 2027.

3.

Lower the fluoroquinolone resistance159 of E. coli to 1% or less in cattle, 2% or less in swine, and 15% or lessin chickens by 2027.

4.

Reduce the total use160 of veterinary antibiotics in the livestock field by 15% from 2020 levels by 2027.

5.

Reduce total use 161 of second-line drugs (third-generation cephalosporins, 15-membered macrolides(tulathromycin and gamithromycin), fluoroquinolones, and colistin) in the livestock field to 27 t or less in 2027.

157 Since tetracycline is the most commonly used antimicrobial in livestock, it has been established since the National Action

Plan on Antimicrobial Resistance (AMR) (2016-2020) was formulated as it reflects the use of antimicrobial agents inlivestock. In this National Action Plan, it will continue to be set from the perspective of continuity. In addition, the antimicrobial
resistance status and sanitary management differ by livestock species, and this National Action Plan sets targets bylivestock species in order to use them as indicators of the results of addressing the issues. The target values are calculated
by using a single regression line to calculate trend values from 2021 to 2027 based on the values from 2012, when timber
harvesting at slaughterhouses and poultry slaughterhouses began, to 2020. In the case of an upward trend toward 2027,
the minimum value obtained between 2016 and 2020 is used as a reference (if the value is 0%, the average of the values
from 2016 to 2020 is used), and in the case of a downward trend, the trend value in 2027 is used as a reference.
158 3rd-generation cephalosporins are important antimicrobial agents in human medicine and are used as second-line
agents in livestock. For this reason, it has been established as one that needs to be monitored in livestock since the National
Action Plan on Antimicrobial Resistance (AMR) (2016-2020) was formulated. Although the target set in the National Action
Plan on Antimicrobial Resistance (AMR) (2016-2020) (to maintain the same level as the Group of Seven (G7) countries)
has been achieved, it will continue to be set from the perspective of continuity. In addition, the antimicrobial resistancestatus and sanitary management differ by livestock species, and this National Action Plan sets targets by livestock species
in order to use them as indicators of the success in addressing the issues. The target values are calculated by using asingle regression line for the trend values from 2012, when timber harvesting at slaughterhouses and poultryslaughterhouses began, to 2027. In the case of an upward trend toward 2027, the minimum value obtained between 2016
and 2020 is used as a reference (if the value is 0%, the average of the values from 2016 to 2020 is used), and in the caseof a downward trend, half of the trend value in 2027 is used as a reference.
159 Fluoroquinolones are important antimicrobial agents in human medicine and are used as second-line drugs in livestock.
For this reason, it has been established as one that needs to be monitored in livestock since the National Action Plan on
Antimicrobial Resistance (AMR) (2016-2020) was formulated. Although the target set in the National Action Plan on
Antimicrobial Resistance (AMR) (2016-2020) (to maintain the same level as the Group of Seven (G7) countries) has beenachieved, it will continue to be set from the perspective of continuity. In addition, the antimicrobial resistance status andsanitary management differ by livestock species, and this National Action Plan sets targets by livestock species in order to
use them as indicators of the success in addressing the issues. The target values are calculated by a single regression line
for the trend values from 2012, when timber harvesting at slaughterhouses and poultry slaughterhouses started, to 2027.
In the case of an upward trend toward 2027, the minimum value obtained between 2016 and 2020 is used as a reference(if the value is 0%, the average of the values from 2016 to 2020 is used), and in the case of a downward or flat trend, halfof the trend value in 2027 is used as a reference.
160 Antimicrobial agents are not set in the National Action Plan on Antimicrobial Resistance (AMR) (2016-2020) from theperspective that antimicrobial agents are used in response to disease outbreaks and that indicators indicate the results ofappropriate use of antimicrobial agents. Antimicrobial agents are important materials in the treatment of bacterial infections
in livestock, and it is necessary to develop a situation in which they can be used when necessary and obtain the desired
effect in the future, and in recent years, as the EU and other countries have been promoting measures to reduce the amountof antimicrobial agents used (sold), there is concern that the high amount of antimicrobial agents used (sold) for veterinary
use in Japan compared to other countries will damage the image of the entire agricultural field and lower consumer
confidence in Japan. From this perspective, the amount of veterinary antimicrobials used (sold) in the livestock field has
been newly set as a performance indicator. The target value is set with reference to the sum of the value calculated as theamount that can be reduced by promoting appropriate use in cattle and poultry and the value calculated based on the
reduction achieved in swine as specified in the National Action Plan on Antimicrobial Resistance (AMR) (2016-2020).
161 Among antimicrobial agents for veterinary use, antimicrobial agents important for human medicine are designated as
second-line drugs. Second-line drugs are used only when treatment with first-line drugs is ineffective and are currently
considered the minimum necessary dosage. In order to avoid overuse of second-line drugs by reducing the overall usage(sales volume), the current volume should not be increased and a new target will be set.

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MONITORING AND EVALUATION OF PROGRESS
Progress in each strategy and action, as well as process indices, should be evaluated annually in the framework of
the International Cooperation Ministerial Meeting for Strengthening Measures on Emerging Infectious Diseases. The
outcome indices should be evaluated by issuing the annual Nippon AMR One Health Report (NOAR).

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REFERENCEGLOSSARY•

Antimicrobial Resistance (AMR)
Refers to the phenomenon where antimicrobials (see below) become ineffective, or pharmaceutical effects
decline, against infectious diseases caused by organisms (bacteria, fungi, viruses and parasites).

•

Antimicrobial-resistant organisms (AROs)
Refers to organisms (bacteria, fungi, viruses and parasites) that exert AMR; bacteria that indicate AMR areparticularly referred to as antimicrobial-resistant bacteria.

•

Antimicrobial-resistant genes (ARGs)
Refers to genes and gene groups in a chromosome or plasmid (extranuclear DNA) that cause AMR in
antimicrobial-resistant organisms.

•

Plasmid-mediated antimicrobial-resistant genes (Plasmid-mediated ARGs)
Refers to antimicrobial-resistant genes that are located in extranuclear DNA outside the bacterial nucleus; thesegenes may be transferred AMR to other antimicrobial susceptible bacteria through conjugation. Most
antimicrobial-resistant Gram-negative bacilli that have recently become an issue have these kinds of genes.

•

Horizontal transfer
Refers to the transfer of plasmid through bacterial conjugation, and to the transfer of antimicrobial resistancegenes (ARGs) to originally antimicrobial susceptible bacteria, through mechanisms such as transformation(antimicrobial resistant gene is transferred when DNA isolated from the bacterial cell enters another bacteria)
and transduction (a bacteria is infected by a virus (phage)); Horizontal transfer occurs not only in the same
bacterial species but also across different species.

•

Antimicrobials
Collectively refers to agents that have antimicrobial activity against pathogenic organisms and are used forhumans, animals and agriculture, for the purpose of treating or preventing infectious diseases, or for effectively
utilizing nutrients in animal feeds; Antimicrobials include antimicrobials used for humans, as well as
antimicrobials used for animals and in agriculture. Antimicrobials for humans include antibacterial agents(agents with antimicrobial activity against bacteria; includes antibiotics and synthetic antibacterials), antifungal
agents, antiviral agents and antiparasitic agents. Veterinary antimicrobials include antibiotics for animals(agents with antimicrobial activity against bacteria; includes antibiotics and synthetic antibacterials), antifungal
agents, antiviral agents and antiparasitic agents used for animals. Antibiotics for animals include both veterinary
antibiotics used for treating veterinary infectious diseases and antibiotic feed additives used for the effective
utilization of nutrients in feeds.

•

Selection pressure
Refers to pressure applied toward the survival of selected antimicrobial-resistant organisms, resulting from theelimination of organisms that are susceptible to a certain agent by using that agent; Among various mechanismsof AMR, selection pressure is one of the largest inducing factors.

•

One Health approach
Refers to a concept where the public health sector, the animal health sector, the environmental health sector,
and other related sectors pursue collaborative and integrated response to infectious diseases that are caused
through complicated interaction among humans, animals, the environment and other factors; With respect to
AMR countermeasures, it has been pointed out that, when antibiotics and other antimicrobials are used in thepractice of medicine, long-term care, veterinary medicine, livestock and aquaculture, agriculture, etc., AROs
that are selected through the use of such agents, as well as genes that cause AMR (ARGs), may be transferredto humans via food chain and the environment. This indicates the necessity of collaborative efforts by these
sectors.

•

Surveillance
To conduct periodic surveys for grasping the actual status of an issue, thereby identifying trends and detectingchanges.

•Monitoring
To conduct periodic surveys to determine whether any corrective actions are required.
National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 88•Japan Nosocomial Infections Surveillance (JANIS)
A surveillance project for identifying trends in the AMR of organisms detected in medical institutions that havebeds under the control of the Ministry of Health, Labour and Welfare (MHLW); Participation in this project isvoluntary. A surveillance report on the analysis of trends in AMR in each institution is provided to theparticipating medical institutions. Open Reports that indicate national trends in AMR are disclosed to the public.

•

Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM)
A system of the Ministry of Agriculture, Forestry and Fisheries (MAFF) for monitoring AMR in livestock andaquaculture and the amounts of sales of veterinary antibiotics; The system is implemented by the National
Veterinary Assay Laboratory (NVAL) as the core laboratory, in collaboration with the prefectural governments,
the Food and Agricultural Materials Inspection Center (FAMIC), fisheries research and laboratory facilities andother related institutions. The results of surveillance and monitoring are published every year in Japanese, andevery few years in English.

•

Healthcare-associated Infection (HAI)Collectively refers to infectious diseases associated to medical intervention; Major healthcare-associatedinfections (HAIs) include catheter-related blood stream infections(CRBSIs), catheter-associated urinary tract
infections (CAUTIs),
surgical site infections(SSIs), ventilator-associated pneumonia (VAP), and Clostridium difficile infections(CDIs). By conducting hospital-based surveillance for these infections, disease burden of AMR in a hospitalcan be measured.

•

Antimicrobial Susceptibility Test
A test for determining whether or not specific pathogenic organisms (bacteria or fungi) are susceptible to an
antibacterial or antifungal agent (i.e. whether or not an agent is effective on specific organisms); when apathogenic organism is able to develop in an environment that exceeds the pre-determined agent
concentration ("breakpoint"), the organism is classified as "resistant". A list that indicates the rates ofsusceptibility to each antimicrobial agent, classified by the type of organism, is called "antibiogram".

•

Antimicrobial Use (AMU)
Indicator for the amount of use of an antimicrobials; because it is impossible to directly compare the amounts
of use, the number of persons, the days of administration, the Antimicrobial Use Density (AUD), and the Daysof Therapy (DOT) are used. For the animal field, it indicates the amount of antibiotics intended to be used, andfigures given by correcting the amount administered, the amount of sales of agents, feeding volume by the
number of animals and average body weight.

•

Antimicrobial Use Density (AUD)
One of the standard indicators for measuring AMU for humans; AUD indicates daily AMU per day per 1,000
or 100 population. Because the Defined Daily Dose (DDD) varies by agent, the total pure powder consumed isdivided by DDD, and is further divided by the total days of administration in the target population.

•

Days of Therapy (DOT)
One of the indices for measuring AMU for humans that was developed by the U.S. Centers for Disease Control
and Prevention (CDC), and is mainly used in developed countries; Unlike AUD, DOT only evaluates the daysof administration of antimicrobials, regardless of the amount of use per day.

•AMR diagnostics
The diagnosis of AMR is mainly performed through phenotypic testing (antimicrobial susceptibility testing) or
genotypic testing (typing of (the products of) antimicrobial resistance genes (ARGs)). While phenotypic testingevaluates the reactivity of organisms to actual agents, genotypic testing evaluates specific antimicrobial
resistance genes (ARGs) and their products (proteins).
Genotypic testing contributes to determination whether certain AMR has been vertically or horizontallytransferred.

•

Codex Alimentarius Commission
The Codex Alimentarius Commission is a global intergovernmental organization established by the Food andAgriculture Organization (FAO) and the World Health Organization (WHO) in 1963, for the purpose ofprotecting the health of consumers and guaranteeing the fair trade of food. The Commission develops
international food standards (Codex standards), etc. Japan joined the Commission in 1966.

National Action Plan on Antimicrobial Resistance (AMR) (2023-2027) | 89•Livestock Health Inspector
Those appointed by prefectural governors pursuant to Article 53, Paragraph (3) of the Act on the Prevention of
Infectious Diseases in Livestock from among prefectural officials who are veterinarians in order to have themengage in the affairs provided for in the Livestock Infectious Disease Prevention Act. However, whenparticularly necessary, the prefectural governor shall appoint a veterinarian other than a veterinarian who is an
official of said prefecture and who has knowledge and experience in the prevention of infectious diseases ofdomestic animals.

•

Fish Epidemic Prevention Officer
Those appointed by prefectural governors from among prefectural employees to engage in the affairs of
prevention of infectious diseases of aquaculture aquatic animals and plants in accordance with paragraph 1 of
Article 13 of the Sustainable Aquaculture Production Assurance Act (Act No. 51 of 1999).

•

Biosecurity Standards
The standards to be observed by livestock owners with respect to sanitary management methods pertaining to
the keeping of livestock, in accordance with Article 12-3 of the Act on the Prevention of Infectious Diseases in
Livestock.

•

World Organisation for Animal Health (WOAH) Collaborating Centres
Inspection and research laboratories accredited by the World Organisation for Animal Health (WOAH) for
scientific knowledge and technical assistance related to animal health.

•

Second-line drugs in the livestock field
Antimicrobial agents to be used in livestock used only when first-line drugs are ineffective. Second-line drugs
are designated based on the results of the risk assessment of antimicrobial resistant bacteria by the Food Safety
Commission (FSC) (assessment of the likelihood and extent to which antimicrobial resistant bacteria selected
through the use of antimicrobial agents in livestock and other food animals can spread to humans via food andaffect their health).

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