AMR Alliance Japan Recommendations
Setting Appropriate Outcome Indices in the Next AMR Action Plan
October 18, 2021
Globally, antimicrobial resistance (AMR) leads up to 700,000 deaths annually. In Japan, an estimated8,000 people die annually from just bloodstream infections caused by two major AMR infections –methicillin-resistant Staphylococcus aureus and fluoroquinolone-resistant Escherichia coli. To preventthe spread of AMR, in April 2016, the Government of Japan enacted the “National Action Plan on
Antimicrobial Resistance 2016-2020 (NAP 2016-2020).” The NAP 2016-2020 has been fundamental inestablishing AMR measures, and has contributed to actions such the collection of AMR related data.
Aiming to review this progress, AMR Alliance Japan held a roundtable expert discussion on the NAP
2016-2020. During this discussion, experts raised points to consider when setting outcome indicesand numeric targets in the upcoming version of the National Action Plan on Antimicrobial Resistance(the “next NAP”). This discussion led to the recommendations described below.
This proposal consists of three sections. First, this proposal provides an overview of the outcome
indices and corresponding numerical targets described in the NAP 2016 – 2020. Second, this proposal
presents an intellectual framework for setting outcome indices and numerical targets in the next NAP.
Third, based on this framework, specific outcome indices are provided for the human, animals, food,and environmental sectors.
The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has demonstrated the importance of
infectious disease policy, and accordingly, there are high expectations for the next NAP. It is hopedthat this proposal can help with the formulation of the next NAP, toward the further strengthening of
AMR countermeasures moving forward.

1AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org

◼ Current situation: outcome indices and corresponding numerical targets in theNAP 2016 -2020
Human sector
Outcome Indices

Numerical targets

Penicillin-resistance rate of Streptococcus pneumoniae in 2020

15% or below

Methicillin-resistance rate of Staphylococcus aureus in 2020

20% or below

Quinolone-resistance rates of Escherichia coli in 2020

25% or below

Carbapenem (Imipenem)-resistance rate of Pseudomonas

10% or below

aeruginosa in 2020
Carbapenem-resistance rate of Escherichia coli and Klebsiella

0.2% or below

pneumoniae in 2020
Daily antimicrobial use per 1000 inhabitants in 2020

Reduced to two-thirds of2013 levels

Daily antimicrobial use per 1000 inhabitants of oral cephalosporins,

Reduced by 50% fromfluoroquinolones, and macrolides in 20202013 levels

Daily intravenous antimicrobial usage per thousand population in

Reduced by 20% from2020

2013 levels

Animal sector
Outcome Indices
Tetracycline-resistance rate of Escherichia coli

Numerical targets

Third-generation cephalosporins-resistance rate of Escherichia coli

Meet level of G7 members

33% or lessin 2020

Fluoroquinolone-resistance rate of Escherichia coli

Meet level of G7 members
in 2020

2AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org

■Future directions: intellectual framework for setting outcome indices and numerical targets inthe next NAP
Outcome indices and numerical targets in the NAP 2016 – 2020
⚫ An analysis should be carried out on trends in antimicrobial resistance rates and antimicrobial use
for each bacterial species throughout the NAP 2016-2020 timeframe. This should include analysisof the relationship between antimicrobial use and resistance rates, and the relationship between
oral antimicrobial and intravenous antimicrobial use in the human sector. This analysis shouldtake place on a rolling basis, and outcome indices in the next NAP should be set and revised inaccordance with analysis results. It is also important to ensure that numeric targets be set basedon evidence.
⚫ Numeric targets are not set with the purpose of simply reducing the total volume of
antimicrobials used – they are set to discourage inappropriate antimicrobial usage.
Inappropriate antimicrobial use must be discouraged while encouraging appropriate use. For thisreason, it would be better to avoid setting targets excessively low.
⚫ Diagnostic tests are indispensable for distinguishing between the proper and improper use of
antimicrobials. Point-of-care testing (POCT) should be promoted concurrently with numericaltargets in order to evaluate the appropriate use of antimicrobials and to encourage antimicrobial
stewardship.
Outcome indices and numerical targets for the next NAP⚫ Numerical targets in the next NAP should be set based on data and other information that has
been collected up to this point. In addition, it would be best to include longer-term, five year andout targets alongside regular numerical targets.
o Examples of extant data sources in each sector:▪

Human sector: Japan Nosocomial Infections Surveillance (JANIS), AMR Bacteria
Bank, National Epidemiological Surveillance of Infectious Disease (NESID), Japan
Antimicrobial Resistance Bacterial Surveillance (JARBS), Japan Surveillance for
Infection Prevention and Healthcare Epidemiology (J-SIPHE), Surveillance for Trend
in Antimicrobial Use.

▪

Animal sector: Japanese Veterinary Antimicrobial Resistance Monitoring System(JVARM), Survey on Methicillin-Resistant Staphylococcus aureus (MRSA)
Infiltration, Survey on Antimicrobial Resistance Trends Expanded to All Cultured
Fish Species, Survey on Antimicrobial Resistance in Pets.
3AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org

⚫ Furthermore, the next NAP should include indicators that assess behaviors at each stage of AMR
control measures (“process indicators”) and indicators that assess the final results of AMR
control measures (“outcome indicators”) in line with each long- and short-term target.
⚫ When setting each indicator and target, it is important to recognize that there are regionalvariations in antimicrobial use and the distribution of antimicrobial resistant bacteria.
Consideration should be given to frameworks for information collection, evaluation, andassessment on a prefecture, primary or secondary care area, healthcare institution, orprescriber basis.
⚫ The setting of indicators and targets in itself helps to communicate the necessity of action andimportance of AMR countermeasures. To facilitate such communication, it is important that eachindicator and target be simple and exceptionally easy to understand.
⚫ Consideration should be given to the construction of a system to research and collect informationon the incidence of community-acquired antimicrobial resistant infections, the prevalence of
healthy carriers of antimicrobial-resistant organisms, the cost of AMR measures, and the impactof AMR on socioeconomic activities.
Ensuring the next NAP contains a One Health perspective spanning the human, animal, andenvironmental sectors⚫ Efforts should be made to comprehensively assess and analyze the state of AMR organisms in
the human, animal, and environmental sectors. It is important to conduct appropriate risk
assessments of organisms originating from the animal and environmental sectors that may impact
human medicine and health. Furthermore, consideration should be given to the creation of aframework for the occasional review and revision of indicators and targets in the NAP toappropriately reflect any risks discovered through such assessments.
⚫ Japan imports many food products, including ingredients that go toward the production frozen

foods and other products. In light of that, efforts should be taken to establish effective
monitoring methods that can determine whether AMR organisms are being imported fromabroad via food.
Please note, the term “animal sector” in this document mainly refers to livestock for humanconsumption (cows, pigs, chicken), fish, and pets.

4
AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org

■Specific recommendations: outcome indices for the next NAP
The following items are proposed as outcome indices in the next NAP based on the considerations
listed above, continuity with the NAP 2016 – 2020, and the ultimate objective of AMR
countermeasures.
End Goals
o Lower number of patients infected with antimicrobial resistant organisms (based onNESID)
o Lower number of deaths from antimicrobial resistant infections (based on vital statistics)
Human sector (1/2): Recommendations based on continuity with the previous NAP
Process indicators: The following indicators should be established in light of the major role that
antimicrobials play in the treatment of infectious diseases in clinical settings. Since the use of
antimicrobials varies from region to region, a system should be established that can analyze andevaluate these indicators on a prefecture, primary or secondary care area, healthcare institution, andprescriber basis.
o Daily use of antimicrobials per 1000 inhabitants (based on data from Japan Antimicrobial
Consumption Surveillance (JACS) and other sources)o Daily use of oral third-generation cephalosporins per 1000 inhabitants (based on datafrom JACS and other sources)o Daily use of oral quinolones per 1000 inhabitants (based on data from JACS and othersources)o Daily use of oral macrolide per 1000 inhabitants (based on data from JACS and othersources)o Daily use of intravenous antimicrobials per 1000 inhabitants (based on data from JACS andother sources)⚫ Outcome indicators: As the situation of antimicrobial resistant organisms varies from region toregion, it will be necessary to establish an analysis and evaluation system that can monitor
antimicrobial resistant organisms nationwide, in primary and secondary care areas, and withineach medical institution. The following indicators should be established in relation toantimicrobial resistance rates and the distribution of antimicrobial resistance.

5AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org

➢ Antimicrobial resistance rate and distribution of penicillin-resistant Streptococcus
pneumoniae (based on data from Japan Nosocomial Infections Surveillance (JANIS) and othersources)➢ Antimicrobial resistance rate and distribution of methicillin-resistant Staphylococcus aureus(based on data from JANIS and other sources)➢ Antimicrobial resistance rate and distribution of quinolone-resistant Escherichia coli (basedon data from JANIS and other sources)➢ Antimicrobial resistance rate and distribution of third-generation cephalosporins-resistantEscherichia coli (based on data from JANIS and other sources)➢ Antimicrobial resistance rate and distribution of carbapenem (imipenem)-resistantPseudomonas aeruginosa (based on data from JANIS and other sources)➢ Antimicrobial resistance rate and distribution of carbapenem-resistant Escherichia coli(based on data from JANIS and other sources)➢ Antimicrobial resistance rate and distribution of carbapenem-resistant Klebsiellapneumoniae (based on data from JANIS and other sources)
Human sector (2/2): Recommendations from the perspective of the end goals of AMR measures⚫

Process indicators: Antimicrobial stewardship is fundamental to AMR countermeasures. To
further promote antimicrobial stewardship, it is important to understand the current status of
inappropriate antimicrobial use, knowledge and behaviors that impact the way the public seeks
and receives medical care, and the extent that AMR countermeasures are being reimbursed by
the Japanese healthcare system. In addition to promoting AMR countermeasures, efforts should
be made to secure more human resources in the field of infectious diseases and promote
appropriate infectious disease countermeasures in general. Based on that perspective, thefollowing indicators should be established.
➢ Percentage of patients with upper respiratory tract inflammation or common cold that aretreated with antimicrobials (based on data from the Health Insurance Claims and Specific
Health Checkups of Japan (NDB) and other sources)➢ Percentage of the public that possesses accurate knowledge on AMR and antimicrobials(based on survey data from the National Center for Global Health and Medicine and othersources)➢ Number of healthcare professionals with professional certifications related to infectious
diseases (based on data from the Japanese Association for Infectious Diseases, the JapaneseSociety of Chemotherapy, the Japanese Society of Hospital Pharmacists and other sources)
6

AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org

➢ Number of reimbursements related to antimicrobial stewardship premiums in the medicalfee system (based on data from NDB and other sources)➢ Number of reimbursements related to antimicrobial stewardship premiums for the pediatricfield in the medical fee system (based on data from NDB and other sources)➢ Number of reimbursements related to regional cooperation for infectious disease control inthe medical fee system (based on data from NDB and other sources)➢ Number of new antimicrobials on the market (based on data from the pharmaceuticalindustry and other sources)
Animal sector (1/2): Recommendations based on continuity with the previous NAP⚫

Outcome indicators: The following indicators should be established to assess the antimicrobial
resistance rate of organisms that could potentially impact human health. In particular,
tetracycline is the most frequently used drug in animals and requires continuous monitoring.
➢ Tetracycline-resistance rate of Escherichia coli in livestock (based on the Japanese Veterinary
Antimicrobial Resistance Monitoring System (JVARM) and other sources)➢ Third-generation cephalosporin-resistance rate of Escherichia coli in livestock (based on
JVARM and other sources)➢ Fluoroquinolone-resistance rate of Escherichia coli in livestock (based on JVARM and othersources)

Animal sector (2/2): Recommendations from the perspective of the end goals of AMR measures⚫

Process Indicators (particularly for livestock): The following indicators should be established inrelation to antimicrobial resistance rates.
➢ Amount of animal-use tetracycline used (based on JVARM and other sources)➢ Amount of animal-use third-generation cephalosporin used (based on JVARM and othersources)➢ Amount of animal-use fluoroquinolone used (based on JVARM and other sources)➢ Amount of colistin used (based on JVARM and other sources)➢ Total use of antimicrobials used in the animal sector (based on JVARM and other sources)⚫

Outcome indicators (livestock): The following indicators should be established to understand theantimicrobial resistance rate of organisms that could potentially impact human health.
➢ Prevalence of methicillin-resistant S. aureus (based on JVARM and other sources)➢ Antimicrobial resistance rate of major bacterial species to fluoroquinolones, third-generation
cephalosporins, colistin, etc. (based on JVARM and other sources)
7

AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org

⚫

Outcome indicators (pets): The following indicators should be established to understand theantimicrobial resistance rate of organisms that could potentially impact human health.
➢ Antimicrobial resistance rate of major bacterial species to fluoroquinolones, third-generation
cephalosporins, etc. (based on JVARM and other sources)⚫

Outcome indicators (fish):➢ Antimicrobial resistance rate of major bacterial species found in fish for human consumption

About AMR Alliance JapanAMR Alliance Japan was established in November 2018 as multi-stakeholder, collaborative organization dedicated to the improvementof public health through the promotion of AMR countermeasures. As of October 2021, its members include, in alphabetical order:Children and Healthcare Project; The Japan Medical Association; The Japan Pharmaceutical Association; The Japan Pharmaceutical
Manufacturers Association; The Japan Society of Hospital Pharmacists; The Japanese Association for Infectious Diseases; The JapaneseSociety for Chemotherapy; The Japanese Society for Clinical Microbiology; The Japanese Society for Medical Mycology; The JapaneseSociety for Pediatric Infectious Diseases; The Japanese Society of Infection Prevention and Control; The Japanese Society of
Pharmaceutical Health Care and Sciences; The Japanese Society of Therapeutic Drug Monitoring; MSD K.K.; Shionogi & Co., Ltd.; Nippon
Becton Dickinson Co., Ltd.; Pfizer Inc.; The Pharmaceutical Society of Japan. The Health and Global Policy Institute serves as theSecretariat of AMR Alliance Japan.
The perspectives described in this document were developed by the AMR Alliance Japan Secretariat reflecting sentiments uncovered
during roundtable discussions held by AMR Alliance Japan on the next NAP. They should not be interpreted as the position of any
individual organization or stakeholder.

8AMR Alliance Japan (Secretariat: Global and Health Policy Institute) https://www.amralliancejapan.org/en/
Grand Cube 3F, Otemachi Financial City, Global Business Hub Tokyo 1-9-2, Otemachi, Chiyoda-ku, Tokyo
TEL: 03-4243-7156 e-mail: info@hgpi.org