Working Group on Regional Information Network on Antimicrobial Resistance, Manila, Philippines, 7-11 December 1987 : report

I (WP)LAB/ICP/CDS!Oll-E 24 March 1988 ENGLISH ONLY WORKING GROUP ON REGIONAL INFORMATION NETWORK ON ANTIMICROBIAL RESISTANCE Convened by the REGIONAL OFFICE FOR THE WESTERN PACIFIC OF THE WORLD HEALTH ORGANIZATION Manila, Philippines 7-11 December 1987 --. Not for sale Printed and distributed by the Regional Office for the Western Pacific of the World Health Organization Manila, Philippines March 1988 ~",. NOTE • The views expressed in this report are those of the participants in the Working Group on Regional Information Network on Antimicrobial Resistance and do not necessarily reflect the policies of the World Health Organization. This report has been prepared by the Regional Office for the Western Pacific of the World Health Organization for governments of Kember States in the Region snd for the participants in the Working Group on Regional Information Network on Antimicrobial Resistance held in Kanila, Philippines, from 7 to 11 December 1987. 1. 2. 3. 4. 5. 6. CONTENTS BACKGROUND . ,. .................................................................................................. .. 1 REVIEW OF THE CURRENT STATUS OF ANTIMICROBIAL RESISTANCE IN COUNTRIES/AREAS OF THE WESTERN PACIFIC REGION ••••••••••••••• 1 2.1 Scope and emphasis of country reports ••••••••••••••••••••• 2 2.2 Summary of country reports ••••••••••••.••••••••••.•••••••• 2 REVIEW OF RESISTANCE SURVEILLANCE, ANTIMICROBIAL SUSCEPTIBILITY TESTING METHODS, INFORMATION SYSTEMS AND POLICIES ON ANTIMICROBIAL UTILIZATION ••••••• ~ •••••••••••••• 3.1 Antimicrobial resistance surveillance information 4 systems in the Western Pacific Region ............................ _'"........ .... 4 3.2 Methods of susceptibility testing in different countries of the Region •••.••••••••••••••••••••••••••••••. 4 3.3 Policies and antimicrobial utilization •••••••••••••••••••• 5 ACTION GUIDELINES ................ ,. .................. ,. ............. ,. .................... ,. ...... .. 5 4.1 Guidelines for a regional information network on antimicrobial resistance ••••••••••••.••••••••••••••.••• 5 4.2 Resolution of problems posed by different· susceptibility testing methods •••••••••••••••••••••••••••• 5 4.3 Guidelines on bacterial species to be reported and on acceptable nomenclature and definition of species ••••••••• 6 4.4 Guidelines on antibiotics tested .•••••.••••••••••••••.•••• 7 RECOMMENDATIONS . ,. .. ,. . ,. .......... ,. .................. ,. ...................... ,. ............ ,. .. REFERENCES .. ,. ............................................................... .. TABLE I - PERCENTAGE RESISTANCE AMONG "INDICATOR ORGANISMS" TO SELECTED ANTIBIOTICS ACCORDING TO THE 7 8 COUNTRIES/ AREAS REPRESENTED • .. • • • •• .. • .. • .. • .. • .. .. • .. • • •• .. • .. 9 TABLE 2 - SURVEILLANCE SYSTEM .................................................... 10 TABLE 3 - METHODS OF SUSCEPTIBILITY TESTING IN DIFFERENT COUNTRIES/AREAS .. .. .. .. .. .. • .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. • • .. .. .. .. • .. .. .... .. ...... 11/12 ANNEX I - LIST OF MEMBERS, TEMPORARY ADVISERS AND SECRETARIAT .. 13 ANNEX 2 - TIME TABLE ................................................................................. 17 1 • BACKGROUND In 1981 and 1982, WHO consultations on the surveillance of antimicrobisl resistance were held in Geneva (!, ~). Theae groups recognized the threat posed by antimicrobial-resistant bacteria in all countries and noted the absence of a coordinated programme to determine the extent of the problem on a global scale, to establish whether there are significant regional differences in the prevalence of resistant bacterial strains and to define the rate of evolution and mechanisms of resistance. They recommended that WHO promote and facilitate surveillance activities at both national snd regionsl levels. They also stressed the necessity for unification of methodology used for surveillance. In 1984 and 1985, the Regional Office for the Western Pacific of the World Health Organization convened meetings of the Scientific Groups on 'the Control of Bacterial Resistance (1, !). These groups recommended that WHO should: (1) develop and promote guidelines for antimicrobial therapy; (2) facilitate the participation of Member States in a surveillance programme of bacterial resistance. A draft manual of antimicrobial guidelines was prepared by the second of these scientific groups. The present Working Group on the Regional Information Network on Antimicrobial Resistance (RINAR) was convened to advise on the establishment of a regional information network of antimicrobial resistance. The objectives of the Working Group were: (a) to review the current status of antimi~robial resistance; (b) to review antimicrobial susceptibility testing methods and information systems in the countries of the Region; (c) to review national policies on antibiotic utilization; (d) to develop guidelines for a regional information network on antimicrobial resistance. The Group elected Dr Makoto Ohashi, Chairman; Dr Mediadora Saniel, Vice-Chairman; and Dr Selwyn Lang and Dr Mavis Yeo, Rapporteurs. The list of temporary advisers and the time table of the meeting are included as Annex 1 and Annex 2, respectively. 2. REVIEW OF THE CURRENT STATUS OF ANTIMICROBIAL RESISTANCE IN COUNtRIES/AREAS OF THE WESTERN PACIFIC REGION Fourteen reports were presented from 12 countries/areas. From the reports, it was observed tbat eacb country bas same kind of local surveillance but tbat not all regularly report on local susceptibility patterns. However, the data are recorded in 108books or in a computer. the - 2 - The "indicator organisms" chosen b}' most prevalence of resistance were as follows: countries/areas to illustrate Cocci Bacilli G + G - 1--------------------------- .!? l'1!'Ben~ §. pneumonia~ enterococci 8.aUreu --- N - .8!'.!!2!E.!!~e B. catarrhalis H. influenza Enterobacte~iaceae !. aeru8i~o8~­ Aci !'.!'!~bac ill .!J? __________________ ....1 The percentage resistance of each organism to every antibacterial was not available for all countries/areas. Percentage resistance among the above "indicator organisms" to selected antibiotics according to the country/area represented is shown in Table 1. 2.2 Summary of country repo~ The country reports on the incidence of antimicrobial resistance are mostly based on hospital laboratory data. The incidence of antimicrobial resistance is sUDDllarized on the basis of the above-mentioned "indica_tor organisms", 2.2.1 Gram positive cocci (1) The information on resistance of .!? l'1!'genes and .!? pne2monia~ to penicillin is not available in all the country reports. But from the available data, it does not seem to be a serious problem in the Region, with the exception of the Philippines where there is occasional resistance of .!? pneumoniae (2%). (2) S. faecalis: Over 70% resistance to ampicillin has been noted in Japan. (3) Beta-lactamase production by S. aureus is the rule in all countries/areas represented. Several c~untries-also have a problem with Methicillin-resistant Staphylococcus aureus (MRSA) which constitute between 0% and 26% of .!? ~2! isolates in particular areas. 2.2.2 Gram negative cocci (1) The prevalence of PPNG ranges from 0.5% to over 50%. Countries/areas where it is a major problem are: Parts of Australia, Brunei Darussalam, the Republic of Korea, Malaysia, the Philippines, Singapore and Hong Kong. - 3 - (2) A majority of !. catarrhal is isolates tested in Japan. the Republic of Korea and New Zealand were found to be resistant to aapicillin (beta-Iactamase production), but the denoainator is often uncertain. 2.2.3 Gram negatIve bacilli (1) The prevalence of beta-lactamase producing H. influenzae variea. In parts of Australia, Malaysia, Singapore and Hong KODa. it was over 15%. (2) In almost all countries/areas represented, a majority of E. coli are now resistant to ampicillin. There is also significant resistance~ cotrimoxazole, and, in the case of isolates in China, the Republic of Korea, Malaysia, Papua New Guinea, the Philippines and Hong Kong, to gentamicin. (3) Gentamicin-resistant Klebsiella !f. are coamon (10-30%) in parts of Australia, China, Republic of Korea, Malaysia. Singapore, Papua New Guinea, the Philippines and Hong Kong. (4) Proteus mirabilis isolates resistant to aapicillin exceed 10% in several areas. (5) Ampicillin resistance among Salmonells species is coaaon but ~. typhi reported in Japan, the Philippines and Singapore reaain susceptible to ampicillin, chloramphenicol and cotrimoxazole. (6) Many Shigella isolates are resistant to ampicillin, but this depends on the species; S. flexneri isolated from China, Japan, the Republic of Korea, Malaysia, the Philippines, Singapore and Viet Ham resistant to ampicillin range from 36%-70%~; In addition, moat of these strains are resistant to a multiplicity of drugs. However,!. sonnei are 1% in the Republic of Korea and 12% in the Philippines. (7) The prevalence of gentamicin-resistant P. aeruginosa varies widely from country to country. (8) Isolates of Acinetobacter ~ from parts of Australia, Brunei Darussalam, the Republic of Korea, MalaYSia, Singapore, the Philippines and Hong Kong are resistant to gentamicin. (9) Tetracycline-resistant vibio cholerae 01 exceed 10% from the isolates of patients in the Philippines. Resistance among anaerobes, e.g., cefoxitin-resistant !. fragilis, beta-lactamase production by!. melaninogenicus was not discussed. Examples of resistsnce among other pathogens not discussed include ~ meningitidis to suphonamides and/or rifampicin and £. jejuni and Legionella penu!phila to erythromycin. Resistance among mycobacteria. c hlamyd is , mycoplasma and fungi was not addressed. This summary necessarily omits much of the resistance data presented at the.eetiac. Data were mostly collected in hospital laboratories. - 4 - 3. REVIEW OF RESISTANCE SURVEILLANCE, ANTIMICROBIAL SUSCEPTIBILITY TESTING METHODS, INFORMATION SYSTEMS AND POLICIES ON ANTIMICROBIAL UTILIZATION 3.1 Antimicrobial resistance surveillance information system. in tbe Western Pacific Region All countries/areas in the Western Pacific Region have some kind of local surveillance but not all regularly give out reports on local susceptibility patterns. However, the data are all recorded in logbooks or in a computer and are available for analysiS as and when required. As shown in Table 2, few countries have a national surveillance system. Since the Central State Laboratory in Brunei Darussalam bandIes 95% of the country's bacteriological specimens and the Department of Pathology in Singapore about 90%, they may be considered to provide a national surveillance system. New Zealand is the only country that actually has an organized national surveillance of selected pathogens with resistant or multi-resistant patterns. Each country recognizes the importance of having its own surveillance scheme and Malaysia hopes to start soon but on a limited scale, i.e. two to three montbs of eacb year, to start with. China and tbe Philippines also hope to establish a national surveillance system sometime in the near future. 3.2 Methods of susceptibility testing in different countries of the Region The modified Kirby-Bauer method is the most frequently used metbod for sensitivity testing in routine clinical bacteriological laboratories 1n the Western Pacific Region. Agar dilution is often used in Australia, Japan, New Zealand and Viet Nam for routine purposes, but is mainly used in other countries for research. In Singapore, agar dilution is used for Neisseria gonorrhoea only. The Stokes and Comparative methods are used 1n Australia, Halaysia, New Zealand and Hong Kong. In these methods, tbe zone size of the test organism is compared directly with the zone size of tbe control organism and the difference in zone sizes will determine whether the organism is susceptible, resistant or intermediate in category. The Australian calibrated dichotomous disc method is only used in Australia and New Zealand, but not Widely (Table 3). 3.3 Policies and antimicrobial utilization Policies on utilization was the major focus of a SCientific Group on the Control of Antimicrobial Resistance, held in December 1985, which found no set policies in most countries. A set of antibiotic guidelines was produced, which is already being used in various ways. They have been translated and distributed in Viet Nam and are being used as a basis for local modification in Halaysia, the Philippines and Sinsapore. The Group considered that their publication by the WHO Regional Office for the Western Pacific would greatly enhance their established value and increase the return on the resources 80 far invested in their production. - 5 - 4. ACTION GUIDELINES 4.1 Guidelines for a regional information network on antiJlicrobial resistance Having discussed the issues of antimicrobial resistance, susceptibility testing and surveillance schemes now operating in states as well as the scheme currently used in the Pan American Health Organization (PAHO) of WHO, the Working Group unanimoualy made the following action recOlllDlendations. The WHO Regional Office for the Western Pacific abould request ministers of health in countries of the Region to allow laboratories of good standing in each country to participate in a computerized aurveillanee scheme on antimicrobial resistance. Any laboratory generating suitable data ahould be encouraged to participate. The consequent development of expertise would facilitate the establishment of national surveillance progra ... s within individual countries. In general, WHO, through the ministers of health, should decide on which institute within a country should be reaponsible for coordinating tbe collection and snalysis of data from the individual participating laboratories in that country. New computer technology now makes it poasible for individual participating laboratories to analyse their own data for their own use whenever they wish and to forward tbese primary data on computer diskettes to the responsible Institute for national analysis, and for the responsible institute to forward diskettes witb botb prt.ary data and national analyses to regional offices for regional analysis. Summaries of regional surveillance would be then fed back to each country and trends made available to the world. The role of the responsible institute in each country would include also consideration of quality control of bacterial identification and susceptibility testing. n,e member present frca China provided an exa~le of tbe beneficial relstionship between surveillance and quality control. Initially, preparstions for surveillance in China encountered probl ... with tbe quality of svailable susceptibility test discs. An institute in China then worked to improve disc production technology utilizing a consultant supported by the WHO Regional Office. Now, improved discs are being produced and will be used in a progr.... to stsndardize all discs produced in the country. 4.2 Resolution of problems posed by different susceptibiUty testig -methods Various susceptibility testing aethods are used in the Western Pacific Region (reference: Document WHO/LAB/87.l). - 6 - 4.2 .• 1 Disc tes ting In addition to the single disc method recommended by WHO (modified Kirby-Bauer), two other disc aethodS are in use in the Region: <a) Stokes aethod - a self-calibrating aethod in which both control and test organisms are sdjacent to the saae disc. The primary e.timate i. comparison of the zone sizes. <b) Comparative method - a derivation of the Stokes' aethod in which test and control strains are on separate plates. Again the primary estimate is comparison of the zone sizes. 4.2.2 Dilution methods A number of countries use agar or broth dilution for routine purposes. Details of the dilution methods in the Region vary and individual data entry programmes will have to be adjuBted to accept them For the purposes of resistance surveillance, primary quantitative data are preferred to categories of resistance, e.g. sensitive, interaediate or resistant based on the modified Kirby-Bauer method. However, the Group was of the opinion that the internal calibration afforded by the Stokes' method would justify direct recording of results by category, which is comparable to the modified K-B method. Whether thia also applies to the comparative method depends on local quality control. While continuous quality control in a given laboratory is preferred, intermittent sampling in every participating laboratory is necessary. 4.3 Guidelines on bacterial species to be reported and on acceptable nomenclature and definition of species All aerobic and anaerobic isolates on which sensitivity testing has been performed should be reported and the site from which they were isolated should be entered when possible, e.g., blood, CSF, sputum, urine, etc. (It is not envisaged that the scheae will encompass mycobacteria, fungi, chlamydia, mycoplasma, etc.) Bacteria should be identified and named at genus or species level as appropriate in accordance with accepted laboratory methods such as indicated in the second part of the WHO Bench-Level Procedure Manual on Basic Bacteriology <l). Surveillance should cover both routine pathogens submitted by hospital and private laboratories and also organi .. s of particular epid.-iological relevance such as those referred by public health and research laboratories and those of particular importance, e.g.)cause of acute respiratory infections, diarrhoeal diseases snd sex.{ally transaitted diseases. - 7 - 4.4 Guidelines on antibiotics tested The surveillance sche.e should not deteraine the range or types of antimicrobial agents tested by participating laboratories except through a process of education and quality control in those cases where the data collected indicate that the participating laboratory is testing inappropriately. Results on all antimicrobials tested in a laboratory should be included in the survey. regardless of whether they are "routine" or "extras" with respect to the particular type of isolate. S. RECOMMEIIDATIONS (1) At least one laboratory in each country of the Region which will begin to coordinate and file data for the surveillance of resistance to antimicrobial agents should be identified through prescribed channels. (2) These laboratories should be provided with computer software to allow for entry and analysis of routine susceptibility test results. Resources should be provided to modify these programmes in order to give maximum support and minimal disturbance to the routine operations of each laboratory without impairing overall compatibility between data from laboratories in t~is or other WHO regions. (3) Support should be provided for a regional workshop aM _ftpower training on quality control identification and susceptibility testing of bacterial isolates. The workshop should initiate the review and interpretation of computer analysis of early surveillance system data and its correlation with that of other organizations. It should also start to expand the surveillance system by obtaining data from an increasing number of laboratories. (4) Publication of the WHO Guidelines for Antimicrobial Therapy should be expedited as previously recommended (!). (S) Efforts should be made to promote dissemination of information from the growing surveillance network together with the WHO Guidelines for Antimicrobial Therapy in order to improve antibiotic use and thus heslth in the Region. - 8 - 6. REFEaENCES 1. Antimicrobial Ilesiatance Ileport of the SCientific Working Group, Geneva, 23-27 November 1981. 2. Surveillance of Antimicrobial Resistance, Ileport of a Consultation, Geneva, 22-26 November 1982. 3. Scientific Group on the Control of Bacterial Resistance, Manila, Philippines, 26-30 Karch 1984. 4. Scientific Group on the Control of Antimicrobial Resistance, Manils Philippines, 2-6 December 1985. 5. Second Part of the WHO Bench-Level Procedure Manual on Basic Bacteriology WHO/LAB/87.l. T~ 1. PERCENTAGI USISURC! MONG "IIIDICATOI OIGANISIIS- TO SELECTED AlltlllOTtCS ACCORDING TO TIll COUIITRI!S/AUAS RlPIESENTED C 0 ! ft • • z l • • • • Gruai.- Antibiotic· Auatral1. ...... , leeubUc ~ PZ:-oar;ur .. 2!!a Jap •• of Hal·E"· Z •• and 'hlUpplnl. Sin,_pore HO.I~ " ..... ~ £!!!!!!. 'In. holatef 0 0 .... 0 0 0.2 1 2 0 0 0 -'-P. 0-717 0/72 2 2 9 .... 0-941 95 91 16 90 .. 85 75 95 94 85 Hath 3-26 2-12 15 16 0-25 1 2 23 0 .... 5-35 8-38 20-40 0.5-61 1 44-63 34 -'-P. 63 75 60 -. 7-19 0-9 U.S , 15 4 2- 4 20 18 .. . 31-66 50 5% 40 70 69 50 l00! 74 58 65-96 Cotr1. 18-38 17 42 37 15 30 25 10 CeDe. 0-2 1- 2 35 0.4 5 17 2 , 35 18 • .. Cen •• 1-17 0.5 10 0.4 U 17 5 30 21 15 10 I .... 16-25 3 61 2.0 IT 10 841 .... 40 57/0.1· 50 , &411· 5/0· .... 40-70 40 ,'·/1· 36· 70/U· 72 60-10 Ceo •• '-35 1- 8 55 50 ,. 5-40 '0 68 19 344 _to 0-28 24 4t " " 45 25 !be ... bad .... , .... k .... tr'/ •••• ,. ''', •• tad ,. T.bl. 3. ...t coa.t., •• / ....... ad tb • .-dlf'.' I-I ... hod. Tho •• u.l .. tb. 'toke. o • ....... t" .... bad ...... , ... tl, ... or41 .. r •• ulta by .. t ... .,. ""'.b ... c .. pa ••• la to tho .-dillad I-I .. tbod. • .. rceataa. r .. lacaace a.oaa the -''''cator oraaat ... • to •• lectl ••• t"'otic. 'I &Ceo~lac to thl couatr1ea/ar ••• r.'I' •••• t ... •. hi" ... o ..... lata ... laol.tad. - .... 'eoc .... carl'W out. - 10 - TABLE 2. SUIlVEILLANCE SYSTEM Country/area National State Local - l. Australia Nil Yes (some) Yes 2. Brunei Daruasala .. Yes (95%) Yes Noregular report 3. China Yes Yes Quarterly reports 4. Japan Yes· Nil Yes So_ give regular reports. 5. Republic of Yes Nil Yes Regular .. onthly Korea selected pathogens reports 6. Malaysia Nil Nil Yes Local journals and To start syaposiUIIIs 7. New Zealand Yes Yes Quarterly selected pathogens bulletins 8. Papua New Nil Yes Some give regular Guinea reports. 9. Philippines Nil Nil Yes No regular reports Hope to start 10. Singapore Yes (90%) Yes So .. e give regular reports. 11. Hong Kong Nil Yes Regular report 12. Viet Na .. Yes Yes (some) Yes No regular reporta selected pathogens *All pathogens in selected lsboratories. All !. typh1. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. - 11/12 - TABLE 3. MEt1IODS OF SUSCEPTIBILITY TESTUIG III IIIPf'UBIIT C:OUlft'aIK'/AUAS Count!)!/area Australia Brunei Darussal .. China Japan Republic of Korea Halaysia New Zealand Papua New Guinea Philippines Singapore Hong Kong Viet Na. TOTAL Index R Research. BP Breakpoint. Stokes X X X X X 5 GC Neisseria lonorrhoeae. !!!£. Mie 8lero Coal!!rative Mod X-B '~i broth dU X X X X X X X X X X R X X R X X B.P X X X R XR X X GC X X 2 7 8 3 X 2 - 13 - ANNEX 1 LIST OF MEMBERS, TEMPORARY ADVISERS AND SECRETARIAT 1. MEMBERS AUSTRALIA Dr Maurice Laurence Mashford Reader in Clinical Pharmacology University of Melbourne Parkville, Victoria 3052 CHINA HOllG KONG JAPAN MALAYSIA Dr Jin Shao Hong National Institute for the Control of Pharmaceutical and Biological Products Temple of Heaven Bei Hng Dr Wilina Wei-ling Lim Medical and Health Officer Clinical Pathology Unit, BJ Queen Elizabeth Hospital Wylie Road, Kowloon Dr S. Mits.uhashi Director Episome Institute Kogure, Fujimi-mura Seta-gun, Gunma Dr Makoto Ohashi Director-General Tokyo Metropolitan Research Laboratory of Public Health 24-1, Hyakunin-cho 3-chome, Shinjuku-ku Tokyo 160 Dr Keizo Yamaguchi Central Clinical Laboratory Naga.aki University 7-1 Slk •• otomachi Nagasaki 852 Dr Cheong Yuet Meng Head of Bacteriology Division Institute for Medical Research 50588 Ku.ls Lumpur Annex 1 NEW ZEALAND PAPUA NEW GUINEA PHILIPPINES REPUBLIC OF KOREA SINGAPORE VIET HAM - 14 - Dr Selwyn Lang Clinical Microbiologist-In-Charge Middlemore Hospital Private Bag Otahuhu, Auckland 6 Dr D. Barua Pathologist In Charge National Health Laboratory Service Department of Health P.O. Box 399 Hohola Boroko Dr Mediadora Saniel Director Research Institute for Tropical Medicine Alabang, Muntinlupa Metro-Manila Dr Yunsop Chong Associate Prof~s~or Department of Clinical Pathology Yonsei University College of Medicine C.P.O. Box 8044 Seoul Dr Mavis Yeo Medical Specialist Ministry of Health College of Medicine Building 16 College Road Singapore 0316 Dr Dao Dinh Duc Head Department of Infectious Disease. Bach Mai Hospital Hanoi - 15/16 - Annex 1 2. TEMPORARY ADVISER UNITED STATES OF AMERICA Dr Thomas F. O'Brien Director, Microbiology Laboratory Brigham and Women's Hospital and Associate Professor of Medicine Harvard Medical School 75 Francis Street Boston, Massachusetts 02115 3. SECRETARIAT Dr Sima HuHan (Operational Officer) Regional Adviser in Health Laboratory Services WHO Regional Office for the Western Pacific Manila Dr T. Imai Computer Systems Analyst WHO Regional Office for the Western Pacific Manila Dr H. Mehta Regional Adviser in Communicable Diseases WHOltegional Office for the Western Pacific Manils TtHE tAIL! !l!!. "'!YE. 7 ~ber ru.lttaZ •• Dec: ..... r Wed ..... !., , Dec .. ber tbure'''Z. 10 DIo.-.. .!nJ!J' • 11_ Dec .... r !!!!!. IF ... l!!!!. !!!!!. It._ 0130 1. ... tetratloft I . 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