19 October 2017

SAVE antibiotics, SAVE children
Challenges to tackle antimicrobial resistanceYoshiaki Gu, MD, MPH, PhD
AMR Clinical Reference Center
National Center for Global Health and Medicine Hospital

Alexander Fleming (1881-1955)

It is not difficult to make microbes resistant to penicillinin the laboratory by exposing them to concentrations
not sufficient to kill them, and the same thing has
occasionally happened in the body.
Nobel Lecture, December 11, 1945
http://www.time.com/time/specials/2007/article/0,28804,1677329_1677708_1677828,00.html

Resistance: Tackling a crisis for the health and wealth of nations
The Review on Antimicrobial Resistance Chaired by Jim O’Neill (December 2014)

Resistance: Tackling a crisis for the health and wealth of nations
The Review on Antimicrobial Resistance Chaired by Jim O’Neill (December 2014)

Gross National Income and Resistance

3GC resistant
E. coli

3GC resistant
Klebsiella sp.

MRSA
Alvarez-Uria G et al. Int J Infect Dis. 2016;52:59–61.

Antibiotic Use in Medical CareAntibiotic use and AMR from 1990-2000
in selected countries

WHO: The evolving threat of antimicrobial resistance, Options for action (2012)

The more antibiotics,
the more resistant bacteria.

Global antibiotic
use by class,2000-2010

State of the World’s Antibiotics, 2015.
CDDEP: Washington, D.C.

Percentage change in antibiotic consumption
per capita 2000–2010, by country

State of the World’s Antibiotics, 2015. CDDEP: Washington, D.C.

Gross Domestic Product and Antibiotic use

Japan

Source: Van Boeckel et al. 2014 (based on IMS MIDAS) and World Bank 2015
The Center for Disease Dynamics, Economics & Policy (CDDEP): “The State of the World’s Antibiotics 2015”

Carbapenem retail sales in selected countries,2005–2010 (per 1,000 population)
Pakistan

Egypt
India

Lancet Infect Dis 2013;13:1057-98

Antibiotic pipeline

WHO “The evolving threat of antimicrobial resistance Options for action” (2012)2017/6/6
http://www.theweek.in/features/lifestyle/India-war-against-over-the-counter-antibiotic-abuse.html

2017/4/7
https://thelogicalindian.com/story-feed/opinion/world-health-day-2017/

Antibiotic Use in LivestockESBL Detection Case in Chicken Meat
(Chicken meat purchased at a store in Kanagawa Prefecture)
ESBL-producing bacteria

Ratio of detection

34 samples of domestic minced chicken
ESBL-producing E. coli only

9ESBL-producing E. coli + ESBL-producing P.

4mirabilis
ESBL-producing P. mirabilis only
Total

4
17 (50.0%)

Not detected in 10 samples of domestic pork
Not detected in 6 samples of domestic beef
Japanese Society of Food Microbiology 28: 123-127, 201120

Estimated Annual Antibiotic Usein the United States.

N Engl J Med 2013; 369:2474-2476

Antibiotic consumption in livestock,
ten top countries 2010-2030

State of the World’s Antibiotics, 2015. CDDEP: Washington, D.C.

Emerging Infectious Diseases. 2007;13:1834-1839

Results of Public Private Collaboration inReduction in Usage of Antimicrobials in Animals

THE NETHERLANDS VETERINARY MEDICINES AUTHORITY, Hetty van Beers (2014)

Resistant bacteria in environment

2017/5/11
https://www.weforum.org/agenda/2017/05/bill-gates-is-helping-india-win-its-war-on-human-waste-heres-how

Dissemination of NDM-1 positive bacteria
in the New Delhi environment

Walsh TR et al. Lancet Infect Dis. 2011;11:355-62.

2015

Collaboration under
One Health Approach

National Action Plan on Antimicrobial resistance (AMR) 2016-2020

Antimicrobial stewardshipAntimicrobial (Antibiotic) stewardship• Coordinated interventions toimprove and measureappropriate use of antibiotics– by promoting the selection of theoptimal antibiotic drug regimen– dosing, duration of therapy, routeof administration
Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases
Society of America and the Society for Healthcare Epidemiology of America. 2016

ANTIBIOTIC STEWARDSHIP PROGRAMIntervention• Preauthorization, Prospective Audit & Feedback• Prescriber-Led Review (antibiotic time-outs,stop orders)• Facility-Specific Clinical Practice Guidelines for
Common Infectious Diseases• Target Patients With Specific Infectious Diseases
Syndromes• Computerized clinical decision support
IDSA, Guideline for Implementing an Antibiotic Stewardship Program

Infection prevention and control

Standard and Isolation Precautions

WHO campaign for hand hygiene

Hand hygiene can decrease
nosocomial infections

1994

1997
Lancet 2000; 356: 1307-12.

Civic Education

Public awareness about antibiotics in Japan(internet survey, Mar 2017)

Antibiotics kill viruses

46.8

Antibiotics are effective against
common cold and influenza

40.6

0%

21.9

24.6

31.3

34.8

20%40%

60%

80%

Yes

No

Don't know

100%

厚生労働科学研究費補助金平成28年度分担研究 医療機関等における薬剤耐性菌の感染制御に関する研究「国民の薬剤耐性に関する意識についての研究」

Public awareness about antibiotics in Japan(internet survey, Mar 2017)

Keep antibiotics at home

11.7

88.3

Have used antibiotics for myself

75.8

Have given antibiotics to family
members or friends

26.5
0%

24.2

73.5

20%

40%
Yes

60%

80%

100%

No

厚生労働科学研究費補助金平成28年度分担研究 医療機関等における薬剤耐性菌の感染制御に関する研究「国民の薬剤耐性に関する意識についての研究」

Field
１

Public awareness/education

２

Surveillance/monitoring

３

Infection prevention/control

４

Proper use of antimicrobial agents５Research & development/drug development

６International cooperation
National Action Plan on Antimicrobial resistance (AMR) 2016-2020

Numeral targets

Human

Proportion of resistant isolates of specific indicator microorganisms
Indicator

2014

2020 (target)

Proportion of penicillin-resistance inStreptococcus pneumoniae

48%

15% or less

Proportion of fluoroquinolone resistance in
Escherichia coli

45%

25% or less

Proportion of methicillin resistance in
Staphylococcus aureus

51%

20% or less

Proportion of carbapenem resistance inPseudomonas aeruginosa

17%

10% or less

Proportion of carbapenem resistance in
Escherichia coli/Klebsiella pneumoniae

0.10.2%

0.2% or less(same level as of 2014)

National Action Plan on Antimicrobial resistance (AMR) 2016-2020

Numeral targets
Antimicrobial Use for humans(average amount of antimicrobials used per day per 1,000 population)
Index

2014

2020 (target)

Total

15.8

Decreased by 33%

Oral cephalosporins, fluoroquinolones,macrolides

11.6

Decreased by 50%

Intravenous antimicrobials

1.2

Decreased by 20%

National Action Plan on Antimicrobial resistance (AMR) 2016-2020

AMR Clinical Reference Center• Established in National Center for Global Health andMedicine Hospital in April 2017

• Working on projects and researches based on National
Action Plan on Antimicrobial Resistance in Japan– Clinical Surveillance Division– Information and Education DivisionAMR Clinical Reference Center

Clinical Surveillance Division• System development for surveillance on Healthcare AssociatedInfection (HAI)• System development for surveillance on Antimicrobial Usage(AMU)• Development of indicators for proper use of antimicrobials andestablishment of surveillanceAMR Clinical Reference Center

Information and Education Division• Creating materials and making PR campaign for raising awareness– For general public, health care workers and public health officials• Creation of guidelines / manuals to support medical practice• Established consortium for infectious disease education topromote these projects

http://amr.ncgm.go.jp/

yogu@hosp.ncgm.go.jp