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. In presenting the results of this surveillance, this report aims to identify the current status of and trends in antimicrobial-resistant bacteria and national antimicrobial use in the areas of human health, animals, agriculture, food and the environment, with the objective of assessing measures to combat antimicrobial-resistant bacteria and clarify challenges in this area.
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. Japan also submits data to the World Organisation for Animal Health (OIE), which uses standardized methods for monitoring the volume of antimicrobial use in animals. 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 IQVIA Solutions Japan K.K. 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 findings by Health and Labor Sciences Research Groups, while the results of a survey by the Japan Livestock Industry Association were used for surveillance of awareness of animal AMR among clinical veterinarians and animal producers.

Results

In Japan, the carbapenem resistance rate in Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae remained below 1% during the observed period, despite its global increase in humans. Likewise, the proportion of vancomycin-resistant enterococci in humans remained less than 1%. Penicillin resistance (non-susceptibility rate) in Streptococcus pneumoniae also has been on the decline in recent years. While the criteria for assessing carbapenem resistance in Pseudomonas aeruginosa changed in 2014, the resistance rate was trending downward. The rate of resistance against the third-generation cephalosporins and fluoroquinolones among Escherichia coli, however, was increasing. Although the percentage of methicillin-resistant Staphylococcus aureus (MRSA) has been declining in recent years, levels remained high. Clear similarities in the pattern of resistance rates to antimicrobials were observed in serotypes of Salmonella spp. isolated from food and from humans, strongly suggesting a link between resistant strains derived from food and from humans.
Usage of antimicrobial agents in Japan based on total sales in 2017 fell by 7.3% from that in 2013 to a defined daily dose per 1,000 inhabitants per day (DID) of 13.8. Oral antimicrobial agents accounted for 90% of total sales, with oral cephalosporins, oral macrolides, and oral fluoroquinolones accounting for the highest shares. While the trend remained similar in 2017, steady progress toward achieving the numerical targets was observed, as the shares of each agent had declined since 2013, by 12.2%, 13.5%, and 9.1% respectively. However, use of parenteral antimicrobials saw a 9.3% increase from 2013.
In food-producing 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 food-producing animals. Tetracycline resistance appeared to be more common, although the degree of resistance depended on animal and bacterial species. Looking at resistance rates specified as outcome indices for the action plan, tetracycline resistance in the indicator bacteria, Escherichia coli derived from healthy animals, fell by approximately 5% from 2014 in 2015. Rates of indicator bacteria resistance to third-generation cephalosporins and fluoroquinolones were also low, remaining mostly below 10% during the observed period. Monitoring of antimicrobial resistance in aquaculture and fisheries began in 2011, focused specifically on the resistance of Lactococcus garvieae (lactococcosis) and Photobacterium damselae subsp. picicida taken from diseased fish (Seriola) and Vibrio parahaemolyticus obtained from aquaculture-environment sampling. This monitoring was extended to cover all farmed fish species from 2017. In the area of companion animals, nationwide surveillance of resistant bacteria isolated from diseased dogs and cats began in 2017. While Escherichia coli isolated from diseased dogs and cats demonstrated lower resistance to tetracyclines and aminoglycosides than those from food-producing animals, resistance rates to fluoroquinolones and cephalosporins tended to be higher.
The volume of sales of antimicrobials used for animals (including food-producing animals, fish and companion animals) was calculated in tons of the active ingredients, based on sales reports for antibiotics and synthetic antimicrobials mandated by the Regulations for Veterinary Drugs (Ordinance of the Ministry of Agriculture, Forestry and Fisheries No. 107 of 2004). These figures showed that sales of antimicrobials for veterinary use rose from 780.88 tons in 2013 to 832.56 tons in 2016. The increase in the volume of sales between 2013 and 2016 was attributed primarily to growth in sales of macrolides (erythromycin used in aquatic animals and 16-membered macrolides used in food-producing animals) and penicillin derivatives, with the rise in erythromycin used in aquatic animals presumed to have been triggered by an outbreak of streptococcal infection. Tetracyclines represented the largest share of antimicrobial sales, accounting for about 40%. In contrast, third-generation cephalosporins and fluoroquinolones each accounted for less than 1% of the total. Usage in each area between 2013 and 2016 was estimated from distribution volumes. Total usage in 2016 was 1,804.3 tons, comprising 591.0 tons for human use, 669.7 tons for food-producing animals, 155.1 tons for aquatic animals, 6.7 tons for companion animals, 228.2 tons for antibiotic feed additives, and 153.6 tons for agrochemicals.

Observations

This year’s report includes data obtained after Japan’s “National Action Plan on Antimicrobial Resistance (AMR) 2016-2020” was published. Figures for 2017 sales of oral antimicrobials, including oral cephalosporins, oral macrolides, and oral fluoroquinolones show that usage of these antimicrobials has fallen overall compared with the data for 2013. In addition, a clear downward trend in antimicrobial resistance rates has emerged among a number of bacterial species, thereby demonstrating progress toward achieving the numerical targets in the action plan. However, resistance rates in Escherichia coli to antimicrobials such as fluoroquinolone continue to climb. The data in this report demonstrate that further promotion of measures against AMR will be required to achieve the targets for 2020. In the case of animals, a rise in sales volumes was observed between 2013 and 2016, caused mainly macrolides (erythromycin used for aquatic animals and 16-membered macrolides used in food-producing animals) and penicillin derivatives, with no substantial increase observed among tetracyclines or the third-generation cephalosporins and fluoroquinolones that are critically important antimicrobials for human medicine. The rate of resistance to the third-generation cephalosporins and fluoroquinolones among Escherichia coli has been kept at a low level. While tetracycline resistance in Escherichia coli fell in 2015 from the year before, further efforts to ensure the prudent use of antimicrobials will be required if the 2020 targets are to be met.

Outcome Indices for the Action Plan
Human-related indices for the Action Plan: proportion (%) of specified antimicrobial-resistant bacteria
2013 2015* 2017 2020(target value†)
Proportion of penicillin-non-susceptible Streptococcus pneumoniae, CSF specimens § 47.4 40.5 29.1 15% or lower
Proportion of penicillin-non-susceptible Streptococcus pneumoniae, non-CSF specimens § 3.2 2.7 2.1
Proportion of fluoroquinolone-resistant Escherichia coli 35.5 38.0 40.1 25% or lower
Proportion of methicillin-resistant Staphylococcus aureus 51.1 48.5 47.7 20% or lower
Proportion of carbapenem-resistant Pseudomonas aeruginosa (Imipenem) 17.1 18.8 16.9 10% or lower
Proportion of carbapenem-resistant Pseudomonas aeruginosa (Meropenem) 10.7 13.1 11.4 10% or lower
Proportion of carbapenem-resistant Escherichia coli (Imipenem) 0.1 0.1 0.1 0.2% or lower
(maintain at the same level)¶
Proportion of carbapenem-resistant Escherichia coli (Meropenem) 0.1 0.2 0.1 0.2% or lowerr
(maintain at the same level)¶
Proportion of carbapenem-resistant Klebsiella pneumoniae (Imipenem) 0.3 0.3 0.2 0.2% or lowerr
(maintain at the same level)¶
Proportion of carbapenem-resistant Klebsiella pneumoniae (Meropenem) 0.6 0.6 0.4 0.2% or lowerr
(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: antimicrobials of use based on sales data (DID)
2013 2013 2017 Change from 2013 2020
(target value*)
Data source Sales† NDB§ Sales Sales
All antimicrobials 14.89 13.25 13.8 7.3%↓ 33%↓
 Oral cephalosporins 3.91 3.44 3.43 12.2%↓ 50%↓
 Oral fluoroquinolones 2.82 2.71 2.57 9.1%↓ 50%↓
 Oral macrolides 4.83 4.55 4.18 13.5%↓ 50%↓
 Intravenous antimicrobials 0.96 0.71 1.05 9.3%↑ 20%↓

DID: Defined daily dose per 1000 inhabitants per day.

Target values were quoted from [1].

Prepared from [2] with partial modification,

Prepared from [3], NDB: national database.

Animal-related indices for the Action Plan: proportion (%) of specified antimicrobial-resistant bacteria
2014* 2015* 2020(target value**)
Proportion of tetracycline-resistant Escherichia coli 45.2 39.9 33% or lower
Proportion of third-generation cephalosporin-resistant Escherichia coli 1.5 0.9 The Same level as in other G7 nations
Proportion of fluoroquinolone-resistant Escherichia coli 4.7 3.8 The Same level as in other G7 nations

Prepared from [35] with partial modification.

JVARM “Results of Monitoring of Antimicrobial Resistant Bacteria Isolated from Food-producing Animals on Farms”.

Target values were quoted from [1].

Way Forward

This document follows on from last year’s report in presenting 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 sales) of human and veterinary antimicrobials. 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. Part of this report includes data obtained after Japan’s “National Action Plan on Antimicrobial Resistance (AMR) 2016-2020” was published. Figures for 2017 show that usage of oral antimicrobials, including oral cephalosporins, oral macrolides, and oral fluoroquinolones is trending downward compared with the data for 2013. However, further promotion of measures against AMR will be required to achieve the 2020 targets.
While an increase in the volume of sales of veterinary antimicrobials was observed between 2013 and 2016, primarily among macrolides and penicillins, resistance among Escherichia coli to third-generation cephalosporins and fluoroquinolones—which are both critically important antimicrobials for human medicine—remained low. In addition, a fall in resistance to tetracycline was observed between 2014 and 2015. Further efforts to ensure thorough adherence to the prudent use of antimicrobials will be required to achieve the targets for 2020.
Comparisons between the volume of antimicrobial use (or sales) in the fields of human medical care, veterinary care, and agriculture were possible for the first time in this report. Major progress was thus seen in such areas as the highlighting of differences in the volume of antimicrobial use in each field by type of antimicrobial, the reporting of antimicrobial resistance rates in diseased companion animals, and the enhancement of data on trends in antimicrobial-resistant bacteria in the area of food. Hopes are high that progress in the surveillance of trends in each field will continue next year and beyond. Furthermore, it is hoped that initiatives of the kind spotlighted by the National Action Plan on Antimicrobial Resistance, focusing on linking data from antimicrobial resistance trend surveillance and monitoring in such areas as human health, animals, and food, will contribute to combating antimicrobial resistance in Japan in the future.

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 additional experts and cooperating governmental agencies:1st meeting on 2/3/2017, 2nd meeting on 3/8/2017, 3rd meeting on 8/21/2017, 4th meeting on 10/2/2017, 5th meeting on 9/5/2018, and 6th meeting on 10/22/2018.

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.

Clinical surveillance 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 Defense 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.

Livestock Technology Department, Kyoto Prefectural Agriculture, Forestry and Fisheries Technology Center

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

Graduate School of Medicine, International University of Health and Welfare

(*Chair)

Additional experts who contributed to this report

Makoto Ohnishi, M.D., Ph.D.

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

Shinya Tsuzuki, M.D., Ph.D.

Department of Hygiene, Graduate School of Medicine, Hokkaido University

Nobuaki Matsunaga M.D., MPH, Ph.D.

AMR Clinical Reference Center, National Center for Global Health and Medicine

Cooperating governmental agencies

Food Safety Commission Secretariat

Ministry of Agriculture, Forestry and Fisheries

Ministry of the Environment

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

Kuniaki Miyake, M.D., MSc.

Director, Infectious Diseases Control Division

Tsuyoshi Inokuchi, M.D., MsPH, Ph.D.

Deputy Director

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

Deputy Director

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

Deputy Director

Norifumi Shigemoto, M.D., Ph.D.

Deputy Director

Satoshi Shimada, M.D., MTM, Ph.D.

Global Infectious Disease Research Officer

Takanori Funaki M.D.

Medical Officer

Kazuhiko Ide M.D., Ph.D.

Medical Officer

Kazuaki Jindai, M.D., MPH

Medical Officer

Ko Iida, M.D.

Medical Officer

Manami Yanagawa, M.D., MTM

Unit Chief

Shiho Yoshii, M.D.

Unit Chief