A statistical information site that deepens
the understanding of AMR (drug resistance) and one health

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A statistical information site that deepens the understanding of AMR (drug resistance) and one health

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The purpose of this Website

Japan’s “National Action Plan on Antimicrobial Resistance (AMR) 2016-2020” was published in April 2016, clearly indicating the implementation of integrated one health surveillance regarding antimicrobial-resistant bacteria that are isolated from humans, animals, food and the environment. This one health surveillance is endorsed as an important strategy for correctly identifying the current status and issues related to AMR, which leads to promoting appropriate national AMR policy. This document is the first surveillance report aimed at identifying the current status and trends of antimicrobial-resistant bacteria and national antimicrobial use in the areas of human health, animals, agriculture, food and the environment.

We hope that this report would provide the first step for presenting Japan's effort to fight against AMR with one health approach to both domestic and international stakeholders; moreover, related governmental agencies, organizations/associations, academic societies and other entities, our intended target readers, are welcome to utilize this report in order to accelerate and advance policy and research activities on AMR.

Background

Japan’s “National Action Plan on Antimicrobial Resistance (AMR) 2016-2020” endorses current status and monitoring of antimicrobial-resistant bacteria and national antimicrobial use as an important strategy for both evaluating the impact of the action plan on AMR and planning future national policy. For global monitoring and reporting, WHO has launched the Global Antimicrobial Resistance Surveillance System (GLASS) for the worldwide gathering and sharing of data on AMR in humans. Japan contributes to GLASS by providing our national data. Accordingly, it is crucial for Japan to show the current status and progress of our AMR policy to not only domestic stakeholders but also the global community in order to accelerate and advance the policy on AMR.

Method

The AMR One Health Surveillance Committee, comprised of experts on AMR in the areas of human health, animals, food and the environment, discussed current surveillance/monitoring systems and reviewed published research on AMR and antimicrobial use. Data on the proportion of antimicrobial resistance among major pathogens in the human medical setting were derived from the Japan Nosocomial Infections Surveillance (JANIS) program organized by the Ministry of Health, Labour and Welfare of Japan. Data on the proportion of antimicrobial resistance among animals and related antimicrobial sales were derived from the Japanese Veterinary Antimicrobial Resistance Monitoring System (JVARM) implemented by the Ministry of Agriculture, Forestry and Fisheries of Japan (MAFF). Moreover, we obtained data on sales and consumption of antimicrobials for human use from the Japan Antimicrobial Consumption Surveillance (JACS) program and the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Data on the distribution of antimicrobial feed additives were provided by the Food and Agricultural Materials Inspection Center (FAMIC) and the Japan Scientific Feeds Associations (JSFA). Data on the amount of domestic shipment of antimicrobials used as agricultural chemicals was from MAFF. Data on antimicrobial resistance patterns of pathogens, which are not monitored by current surveillance and monitoring systems but considered pertinent from a public health perspective, and public awareness toward AMR were obtained from individual published research. The latest data available, mostly up to 2015, are included.

Results

In Japan, the proportion of carbapenem resistance in Enterobacteriaceae such as Escherichia coli and Klebsiella pneumoniae remained at around 1% during the observed period, despite its global increase in humans. Likewise, the proportion of vancomycin-resistant enterococci in humans was less than 1%. The proportion of Escherichia coli resistant against the third generation cephalosporins and fluoroquinolones, however, was increasing; and that of methicillin-resistant Staphylococcus aureus (MRSA) accounted for approximately 50%. Penicillin-resistant Streptococcus pneumoniae (PRSP) accounted for approximately 40% of all detected pneumococcus in cerebral spinal fluid samples. Furthermore, oral antimicrobial agents accounted for about 90% of the total sales in Japan. Among all oral antimicrobial agents sold, rates of defined daily dose per 1,000 inhabitants per day (DID) of cephalosporins, macrolides and quinolones were higher than that of penicillins.

In animals, monitoring of resistant bacteria in cattle, pigs and chickens was conducted. The proportion of antimicrobial-resistant Escherichia coli and Salmonella spp. derived from diseased animals tended to be higher than those derived from healthy animals. It appeared that tetracycline resistance was more common, although the degree of the resistance depended on animal and bacterial species. The proportion of third generation cephalosporin- and fluoroquinolone-resistant Escherichia coli, the indicator bacteria, derived from health animals, was low and remained mostly less than 10% during the observed period. Monitoring of antimicrobial resistance in aquaculture and fisheries has been conducted since 2011: specifically, the resistance of Lactococcus garvieae and Photobacterium damselae subsp. picicida taken from diseased fish (Seriola) and Vibrio parahaemolyticus obtained from aquaculture-environment sampling. The sales volume of antimicrobials used for animals including food-producing animals, fish and companion animals was calculated in tons of the active ingredients, which were based on the sales volume of antibiotics and synthetic antimicrobials mandated by the Regulations for Veterinary Drugs (Ordinance of the Ministry of Agriculture, Forestry and Fisheries No. 107 of 2004). The antimicrobials sales volume for veterinary use appeared to be decreasing over the years, with figures of 854.50 tons, 793.75 tons and 780.88 tons for 2009, 2011 and 2013, respectively. Tetracyclines represented the largest share of total antimicrobial sales volume, accounting for about 40%, whereas both the third generation cephalosporins and fluoroquinolones were less than 1% of the total sales volume.

Conclusion

The use of cephalosporins and quinolones and the proportion of resistance to those antimicrobials were higher in humans. In contrast, tetracyclines were more commonly used in animals and tetracycline resistance was high among animals. Overall, the surveillance and monitoring of antimicrobial resistance in human and animals are well established in Japan, whilst there is still much to be desired in terms of comprehensive monitoring systems for the environment and food. Further discussion is needed for new surveillance and monitoring systems in those areas. Regarding the current, already-implemented surveillance and monitoring systems, further discussions for new methods of analyses considering bias, enhancement of quality assurances and inter- surveillance comparisons are needed in order to improve the accuracy of those systems. By addressing each challenge, we hope that our effort can help uncover mechanisms and inter- connectivity with regard to the development and transmission of antimicrobial resistance among humans, animals, agriculture, food and the environment.

Outcome Indices for the Action Plan
Human-related indices for the Action Plan: proportion (%) of specified antimicrobial-resistant bacteria
2015* 2020
target value†
Proportion of penicillin-non-susceptible Streptococcus pneumoniae, CSF specimens § 40.5 15% or lower
Proportion of penicillin-non-susceptible Streptococcus pneumoniae, non-CSF specimens § 2.7 15% or lower
Proportion of fluoroquinolone-resistant Escherichia coli 38.0 25% or lower
Proportion of methicillin-resistant Staphylococcus aureus 48.5 20% or lower
Proportion of carbapenem-resistant Pseudomonas aeruginosa (Imipenem) 18.8 10% or lower
Proportion of carbapenem-resistant Pseudomonas aeruginosa (Meropenem) 13.1 10% or lower
Proportion of carbapenem-resistant Escherichia coli (Imipenem) 0.1 0.2% or lower
(maintain at the same level) ¶
Proportion of carbapenem-resistant Escherichia coli (Meropenem) 0.2 0.2% or lower
(maintain at the same level) ¶
Proportion of carbapenem-resistant Klebsiella pneumoniae (Imipenem) 0.3 0.2% or lower
(maintain at the same level) ¶
Proportion of carbapenem-resistant Klebsiella pneumoniae (Meropenem) 0.6 0.2% or lower
(maintain at the same level) ¶

CSF, cerebrospinal fluid

Prepared based on JANIS data

Target values were quoted from the National Action Plan on Antimicrobial Resistance (AMR).[1]

The proportion of penicillin-non-susceptible Streptococcus pneumoniae in 2014, as indicated in the Action Plan, is based on the CLSI (2007) Criteria where those with penicillin MIC of 0.125 μg/mL or higher are considered resistant. The CLSI Criteria were revised in 2008, applying different standards to CSF and non-CSF specimens. Based on this revision, JANIS has divided data into CSF and non-CSF specimens since 2015.

The National Action Plan on Antimicrobial Resistance (AMR) [1] indicates that the respective proportion of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae were at 0.1% and 0.2% in 2014, and the proportions should be maintained at the same level in 2020.

Human-related indices for the Action Plan: volume of use and sales of antimicrobials (DID)
2013 2013 2020 (target value*)
Data used Volume of sales † NDB §
All antimicrobials 15.80 14.00 Reduce by 33%
Oral cephalosporins 3.85 3.09 Reduce by 50%
Oral fluoroquinolones 2.75 2.61 Reduce by 50%
Oral macrolides 4.84 4.82 Reduce by 50%
Intravenous antimicrobials 1.23 0.83 Reduce by 20%

DID: Defined daily dose per 1000 inhabitants per day

Target values were quoted from [1].

Prepared from [2] with partial modification

Adpated from [3] [4] with partial modification

Animal-related indices for the Action Plan: proportion (%) of specified antimicrobial-resistant bacteria
2014 2020 (target value*)
Propotion of tetracycline-resistant Escherichia coli 45.2 33% or lower
Proportion of third-generation cephalosporin- resistant Escherichia coli 1.5 The Same level
as in other G7 nations
Proportion of fluoroquinolone-resistant Escherichia coli 4.7 The Same level
as in other G7 nations

Target values were quoted from [1].

Way Forward

This document is the first report in Japan, representing information on the current status of antimicrobial resistance in the areas of human health, animals, agriculture, food and the environment, as well as the volumes of use (or of sales) of human and veterinary antimicrobials. It is a great achievement to compile those data into one report. This report also featured the special monitoring systems in aquaculture and companion animals, proving that a number of monitoring systems that can be globally shared exist in Japan. Based on this current report, it is expected that AMR-related measures will be further advanced by promoting multi-disciplinary cooperation and collaboration. It is also considered crucial to continue with advanced surveillance activities, in order to take the leadership in global policy in AMR.

In contrast, according to the comprehensive collection of information, the current detection status of antimicrobial-resistant bacteria in each area and the current status of use of antimicrobials revealed that the quality of each surveillance was variable. Upon analyzing relationships among different areas regarding the antimicrobial-resistant bacteria and the use of antimicrobials, it is necessary to consider the difference in each area and make the data compatible. The future challenge include standardization of measurement methods, verification of the representativeness of data in each morniting systems, establishment of quality assuarance in each surveillance systems, and continuity of monitoring systems that are conducted as research activities. Further research is warranted to uncover mechanisms and inter-connectivity with regard to the development and transmission of antimicrobial resistance among humans, animals, agriculture, food and the environment.

The Process of Preparation of This Report

This report was drafted through discussion at the a series of the AMR One Health Surveillance committee in cooperation with addtinal expers and cooporating govemental agencies:1st meeting on on 2/3/2017, 2nd meeting on 3/8/2017, 3rd meeting on 3/8/2017, 4th meeting on 8/21/2017, and 5th meeting on 10/2/2017.

Members of the Antimicrobial Resistance (AMR) One Health Surveillance Committee

Tetsuo Asai, D.V.M., Ph.D.

United Graduate School of Veterinary Science, Gifu University

Yuko Endo, Ph.D.

Assay Division II, National Veterinary Assay Laboratory, Ministry of Agriculture, Forestry & Fisheries

Satoshi Kamayachi, M.D.

Japan Medical Association

Makoto Kuroda, Ph.D.

Pathogen Genomics Center, National Institute of Infectious Diseases.

Masato Sakai , D.V.M., M.S.

Japan Veterinary Medical Association

Masumi Sato, D.V.M., Ph.D.

Division of Pathology and Pathophysiology, National Institute of Animal Health, National Agriculture and Food Research Organization

Hiroto Shinomiya, M.D., Ph.D.

Ehime Prefectural Institute of Public Health and Environmental Science

Keigo Shibayama, M.D., Ph.D.

Department of Bacteriology II, National Institute of Infectious Diseases

Hiroaki Tanaka, Ph.D.

Research Center for Environmental Quality Management, Graduate school of Engineering, Kyoto University

Yutaka Tamura, D.V.M., Ph.D.

Center for Veterinary Drug Development, Rakuno Gakuen University

Kayoko Hayakawa, M.D., Ph.D.

Clincial suveillance division, National Center for Global Health and Medicine, AMR Clinical Reference Center

Shuhei Fujimoto, M.D., Ph.D.

Department of Bacteriology and Bacterial Infection, Division of Host Defence Mechanism, Tokai University School of Medicine

Tamano Matsui, M.D., Ph.D.

Infectious Disease Surveillance Center, National Institute of Infectious Diseases

Satoshi Mitarai, M.D., Ph.D.

Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association

Yuichi Muraki, Ph.D.

Department of Clinical Pharmacoepidemiology, Kyoto Pharmaceutical University

Sayoko Yano, D.V.M.,Ph.D.

Kyoto Prefectural Chutan Livestock Hygiene Center

Haruo Watanabe , M.D., Ph.D*

School of Medicine, International University of Health and Welfare; Honorary member, National Institute of Infectious Diseases

(*Chair)

Additional experts who contriubted to this report

Makoto Ohnishi, M.D., Ph.D

Department of Bacteriology I, National Institute of Infectious Diseases

Noriko Konishi, Ph.D.

Division of Food Microbiology, Tokyo Metropolitan Institute of Public Health

Masaki Tanabe, M.D., Ph.D

Department of Infection Control and Prevention, Mie University Hospital

Cooperating governmental agencies

Food Safety Commission Secretariat

Ministry of Agriculture, Forestry and Fisheries

Ministry of the Environment

Secretariat (Tuberclosis and Infectious Diseases Control Division, Health Service Bureau, Ministry of Health, Labour and Welfare)

Kuniaki Miyake, M.D., M.Sc.

Hiroyuki Noda, M.D., Ph.D.

Shunji Takakura , M.D., Ph.D.

Kazuaki Jindai, M.D., M.P.H.

The English version of this report was edited by

Kazuaki Jindai, M.D., M.P.H.; Rieko Takahashi, M.D., M.P.H.; Yasunori Ichimura, M.D., Ph.D.; Shunji Takakura M.D., Ph.D; and Hiroyuki Noda, M.D., Ph.D.
All are affiliated with Tuberclosis and Infectious Diseases Control Division, Health Service Bureau, Ministry of Health, Labour and Welfare.