ANTIMICROBIAL RESISTANCE Global Report on Surveillance 2014 ANTIMICROBIAL RESISTANCE Global Report on Surveillance 2014 WHO Library Cataloguing-in-Publication Data Antimicrobial resistance: global report on surveillance 1.Anti-infective agents - classification 2.Anti-infective agents - adverse effects 3.Drug resistance, microbial - drug effects 4.Risk management 5.Humans I.World Health Organization ISBN 978 92 156474 (NLM classification: QV 250) © World Health Organization 2014 All rights reserved Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: bookorders@who.int) Requests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html) The designations employed and the presentation of the material in this publication not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries Dotted lines on maps represent approximate border lines for which there may not yet be full agreement The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication However, the published material is being distributed without warranty of any kind, either expressed or implied The responsibility for the interpretation and use of the material lies with the reader In no event shall the World Health Organization be liable for damages arising from its use Credits // Cover photo: ©Shutterstock: © Alex011973 / © Allies Interactive / © Fedorov Oleksiy / © Ivan Cholakov / © Michel Borges / © Vlue // Design and Layout: www.paprika-annecy.com Reprinted June 2014 with changes Printed in France IV Contents Foreword IX Summary X Acknowledgements XIV Abbreviations XVI Introduction XIX SECTION O1 Resistance to antibacterial drugs 1.1 Background 1.1.1 Limitations 1.2 Regional surveillance of antibacterial resistance 1.2.1 WHO African Region 1.2.2 WHO Region of the Americas 1.2.3 WHO Eastern Mediterranean Region 1.2.4 WHO European Region 1.2.5 WHO South-East Asia Region 1.2.6 WHO Western Pacific Region 1.3 References SECTION O2 Resistance to antibacterial drugs in selected bacteria of international concern 2.1 Availability of national resistance data 10 2.1.1 Key messages 12 2.2 Resistance data on specific pathogens 2.2.1 Escherichia coli – resistance to third-generation cephalosporins and to fluoroquinolones 2.2.2 Klebsiella pneumoniae – resistance to third-generation cephalosporins and to carbapenems 2.2.3 Staphylococcus aureus – resistance to methicillin 2.2.4 Streptococcus pneumoniae – resistance (non-susceptibility) to penicillin 2.2.5 Nontyphoidal Salmonella – resistance to fluoroquinolones 2.2.6 Shigella species – resistance to fluoroquinolones 2.2.7 Neisseria gonorrhoeae – decreased susceptibility to third-generation cephalosporins 12 12 15 19 21 23 25 27 2.3 References 30 SECTION O3 The health and economic burden due to antibacterial resistance 35 3.1 Methods 35 3.2 Findings 36 3.2.1 Health burden 36 3.2.2 Economic burden 37 3.3 Knowledge gaps 39 3.4 Key messages 40 3.5 References 40 V ANTIMICROBIAL RESISTANCE Global Report on surveillance 2014 SECTION O4 Surveillance of antimicrobial drug resistance in disease-specific programmes 43 4.1 Tuberculosis 4.1.1 Evolution of drug resistance in tuberculosis 4.1.2 Surveillance of drug-resistant tuberculosis 4.1.3 Global public health response to drug-resistant tuberculosis 4.1.4 Notification of MDR-TB cases and enrolment on treatment 4.1.5 Public health implications: treatment outcomes for multidrug-resistant and extensively drug-resistant tuberculosis 4.1.6 Key messages 43 44 44 46 46 4.2 Malaria 4.2.1 Evolution of antimalarial drug resistance 4.2.2 Surveillance of antimalarial therapeutic efficacy and resistance 4.2.3 Global public health implications of antimalarial drug resistance 4.2.4 Key messages 49 49 50 51 51 4.3 HIV 4.3.1 Surveillance of anti-HIV drug resistance 4.3.2 Global public health implications of anti-HIV drug resistance 4.3.3 Key messages 51 52 53 53 4.4 Influenza 4.4.1 Evolution of resistance in influenza viruses 4.4.2 Anti-influenza drug resistance 4.4.3 Surveillance of anti-influenza drug resistance 4.4.4 Public health implications of anti‑influenza drug resistance 4.4.5 Key messages 53 53 54 54 55 55 47 49 4.5 References 55 SECTION O5 Surveillance of antimicrobial resistance in other areas 59 5.1 A ntibacterial resistance in food-producing animals and the food chain 5.1.1 Ongoing surveillance of antimicrobial resistance in food-producing animals and food 5.1.2 Integrated surveillance of antimicrobial resistance in foodborne bacteria 5.1.3 Antimicrobials of particular importance in human and veterinary medicine 5.1.4 Implications for human health from zoonotic transmission of resistant bacteria and genetic material 5.1.5 WHO–FAO–OIE tripartite intersectoral collaboration on action 5.1.6 Key messages 59 59 60 61 61 62 62 5.2 Antifungal drug resistance: the example of invasive Candidiasis 5.2.1 Antifungal drug resistance in Candida species 5.2.2 Antifungal drug resistance surveillance 5.2.3 Magnitude of resistance at a global level 5.2.5 Key messages 62 63 63 64 65 5.3 References 65 SECTION O6 Conclusions 69 6.1 Main findings 6.1.1 Current status of resistance to antibacterial drugs 6.1.2 Burden of resistance to antibacterial drugs 6.1.3 Surveillance of antibacterial resistance 6.1.4 Surveillance and present status of antimicrobial drug resistance in disease-specific programmes 6.1.5 Antibacterial resistance in food-producing animals and the food chain 6.1.6 Resistance in systemic candidiasis 69 69 69 69 70 71 71 6.2 Gaps 71 6.3 The way forward 71 6.4 References 71 VI Annex Methods for collecting data on surveillance and antibacterial resistance ANNEXES 73 A1.1 Definitions 73 A1.2 Data collection from Member States and networks 74 A1.3 Literature search for data in scientific publications 74 A1.4 Reference 75 Annex Reported or published resistance rates in common bacterial pathogens, by WHO region 77 A2 Tables: A2.1-A2.6 A2.7-A2.12 A2.13-A2.18 A2.19-A2.24 A2.25-A2.30 A2.31-A2.36 A2.37-A2.42 A2.43-A2.48 A2.49-A2.54 Escherichia coli: Resistance to third-generation cephalosporins 77-87 Escherichia coli: Resistance to fluoroquinolones 88-96 Klebsiella pneumoniae: Resistance to third-generation cephalosporins 97-102 Klebsiella pneumoniae: Resistance to carbapenems 103-108 Staphylococcus aureus: Resistance to methicillin (MRSA) 109-116 Streptococcus pneumoniae: Resistance, or non-susceptibility, to penicillin 117-126 Nontyphoidal Salmonella (NTS): Resistance to fluoroquinolones 128-135 Shigella species: Resistance to fluoroquinolones 136-142 Neisseria gonorrhoeae: Decreased susceptibility to third-generation cephalosporins 143-149 A2.55 References 150 Annex The burden of antibacterial resistance: a systematic review of published evidence (technical report on methods and detailed results) 169 A3.1 Methods 169 A3.2 Results 171 A3.3 References 206 Appendix Questionnaires used for data collection 221 APPENDICES Ap1.1 Questionnaire and data template for national antimicrobial resistance (AMR) surveillance 221 Ap1.2 Questionnaire and data template for antimicrobial resistance (AMR) surveillance networks 222 Appendix WHO tools to facilitate surveillance of antibacterial resistance 225 Ap2.1 WHONET 225 Ap2.2 Guiding WHO documents for surveillance of AMR 226 Ap2.3 ICD 10 codes for antimicrobial resistance 229 Ap2.4 References 229 Appendix Additional international antibacterial resistance surveillance networks 231 Ap3.1 Networks performing general surveillance of antibacterial resistance 231 Ap3.2 References 232 VII ANTIMICROBIAL RESISTANCE Global Report on surveillance 2014 VIII Foreword Foreword Antimicrobial resistance (AMR) within a wide range of infectious agents is a growing public health threat of broad concern to countries and multiple sectors Increasingly, governments around the world are beginning to pay attention to a problem so serious that it threatens the achievements of modern medicine A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century Determining the scope of the problem is essential for formulating and monitoring an effective response to AMR This WHO report, produced in collaboration with Member States and other partners, provides as accurate a picture as is presently possible of the magnitude of AMR and the current state of surveillance globally Nonetheless, the report makes a clear case that resistance to common bacteria has reached alarming levels in many parts of the world indicating that many of the available treatment options for common infections in some settings are becoming ineffective Furthermore, systematic reviews of the scientific evidence show that ABR has a negative impact on outcomes for patients and health-care expenditures The report focuses on antibacterial resistance (ABR) in common bacterial pathogens Why? There is a major gap in knowledge about the magnitude of this problem and such information is needed to guide urgent public health actions ABR is complex and multidimensional It involves a range of resistance mechanisms affecting an ever-widening range of bacteria, most of which can cause a wide spectrum of diseases in humans and animals Generally, surveillance in TB, malaria and HIV to detect resistance, determine disease burden and monitor public health interventions is better established and experiences from these programmes are described in the report, so that lessons learnt can be applied to ABR and opportunities for collaboration identified WHO, along with partners across many sectors, is developing a global action plan to mitigate AMR Strengthening global AMR surveillance will be a critical aspect of such planning as it is the basis for informing global strategies, monitoring the effectiveness of public health interventions and detecting new trends and threats One important finding of the report, which will serve as a baseline to measure future progress, is that there are many gaps in information on pathogens of major public health importance In addition, surveillance of ABR generally is neither coordinated nor harmonized, compromising the ability to assess and monitor the situation Dr Keiji Fukuda Assistant Director-General Health Security IX ANTIMICROBIAL RESISTANCE Global Report on surveillance 2014 Summary Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi This report examines, for the first time, the current status of surveillance and information on AMR, in particular antibacterial resistance (ABR), at country level worldwide Key findings and public health implications of ABR are: Nevertheless, it is critical to obtain a broad picture of the international scope of the problem of ABR To accomplish this, WHO obtained, from 129 Member States, the most recent information on resistance surveillance and data for a selected set of nine bacteria–antibacterial drug combinations of public health importance Of these, 114 provided data for at least one of the nine combinations (22 countries provided data on all nine combinations) • Very high rates of resistance have been observed in bacteria that cause common health-care associated and community-acquired infections (e.g urinary tract infection, pneumonia) in all WHO regions • There are significant gaps in surveillance, and a lack of standards for methodology, data sharing and coordination Some data sets came from individual surveillance sites, or data from several sources rather than national reports Many data sets were based on a small number of tested isolates of each bacterium (