Antimicrobial Resistance in the Western Pacific …...4 Surveillance of Antimicrobial resistance...

Antimicrobial Resistancein the Western Pacific RegionA Review of Surveillance and Health Systems Response

AMR Final.indd 1 7/4/15 6:07 PM


Antimicrobial Resistancein the Western Pacific Region

A Review of Surveillance and Health Systems Response


WHO Library Cataloguing-in-Publication Data Antimicrobial resistance in the Western Pacific Region: a review of surveillance and health systems response.

1. Drug resistance, Microbial. I. World Health Organization Regional Office for the Western Pacific.

ISBN 978 92 9061 701 3 (NLM Classification: WB 330)

© World Health Organization 2015

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Photo cover: © CDC


Abbreviations ii

Introduction 1

1. SURVEILLANCE OF ANTIMICROBIAL RESISTANCE 3

1.1 AMR surveillance and external quality assurance in the WesternPacificRegion 6

1.2 ProposedregionalAMRsurveillancesystem 10

1.3 QualityassurancestrategiesforAMRsurveillance 18

1.4 GovernanceandownershipofAMRsurveillancedata 20

1.5 SurveillancetosupportcontainmentofAMR 20

2. MONITORING OF ANTIMICROBIAL USE 23

2.1 WHOrecommendationsformonitoringantimicrobialuse 25

2.2 Proposedregionalsystemtomonitorantimicrobialuse 26

2.3 Globalsystemsformonitoringantimicrobialuse 28

2.4 Presentationanddisseminationofsurveillancedata 29

2.5 ChallengesformonitoringantimicrobialuseintheRegion 31

2.6 Thewayforward 32

3. HEALTH SYSTEM RESPONSE TO SUPPORT CONTAINMENT OF ANIMICROBIAL RESISTANCE 33

3.1 Regional-specificchallenges 35

3.2 Improvingregulations 38

3.3 Strengtheninginfection,preventionandcontrol 41

References 47

Table of Contents

i


ii

AGISAR AdvisoryGrouponIntegratedSurveillanceofAntimicrobialResistanceAMR antimicrobialresistanceAPEC Asia-PacificEconomicCooperationASEAN AssociationofSoutheastAsianNationsAST antibioticsusceptibilitytestingATC Anatomical,TherapeuticandChemical(classificationsystem)AVWG WHOExpertWorkingGrouponInfluenzaViralSusceptibilityCLSI ClinicalandLaboratoryStandardsInstituteCSA countrysituationanalysisDDD defineddailydoseEaP EasternPartnershipEARS-Net EuropeanAntimicrobialResistanceSurveillanceNetworkECDC EuropeanCentreforDiseasePreventionandControlEQAS ExternalqualityassurancesystemESAC-Net EuropeanSurveillanceofAntimicrobialConsumptionNetworkEU EuropeanUnionEUCAST EuropeanCommitteeonAntimicrobialSusceptibilityTestingFAO FoodandAgricultureOrganizationoftheUnitedNationsGASP GonococcalAntimicrobialSurveillanceProgrammeGFN GlobalFoodborneInfectionsNetworkGISRS GlobalInfluenzaSurveillanceandResponseSystemGMP goodmanufacturingpracticesGPP goodpharmacypracticeGPRIM GlobalPlanforInsecticideResistanceManagementinMalariaVectorsGPSC GlobalPatientSafetyChallenge(ofWHO)HAI health-care-associatedinfectionHCF health-carefacilityIPC infectionpreventionandcontrolMDR multidrug-resistantMIC minimuminhibitoryconcentrationMRSA methicillin-resistantStaphylococcus aureusNPS NationalPrescribingServiceOECD OrganisationforEconomicCo-operationandDevelopmentOIE WorldOrganisationforAnimalHealthOTC overthecounterPOLHN PacificOpenLearningHealthNetPPTC PacificParamedicalTrainingCentreREQAP RegionalExternalQualityAssuranceProgrammeRCPA RoyalCollegeofPathologistsofAustralasiaRCPAQAS RoyalCollegeofPathologistsofAustralasiaQualityAssuranceProgrammesReLAVR LatinAmericanNetworkforAntimicrobialResistanceSurveillanceSTGs standardtreatmentguidelinesTB tuberculosisUKNEQAS UnitedKingdomNationalExternalQualityAssessmentServiceTWG technicalworkinggroupVINARES VietNamResistance(project)VRE vancomycin-resistantenterococciWePARS WesternPacificAntimicrobialResistanceSurveillance(network)WHO WorldHealthOrganizationXDR extensivelydrug-resistant

Abbreviations


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IntroductionAntimicrobial resistance (AMR) is a global public health threat of high concern intheWesternPacificRegion.The2014WorldHealthAssemblyresolutionWHA67.25stresses the need for urgent action to combatAMR. In theWestern Pacific Region,priority actions to containAMRwere identified by theWorldHealthOrganization(WHO)inconsultationwithMemberStates.TheseactionsareoutlinedintheAction Agenda for Antimicrobial Resistance in the Western Pacific Regionwhichwasendorsedbythesixty-fifthsessionof theRegionalCommittee for theWesternPacific.Theactionagendaprovides a background toAMR in theRegion andhighlights challenges inaddressingthispublichealththreat.

Antimicrobial Resistance in the Western Pacific Region: A review of Surveillance and Health Systems Responseprovidesanin-depthsituationalreviewandtechnicaldiscussioninthreemainareasforthecontainmentofAMRintheRegion:

(1) SurveillanceofAMRintheWesternPacificRegion.(2) MonitoringofantimicrobialuseintheWesternPacificRegion.(3) HealthsystemsresponsetosupportcontainmentofAMRintheWesternPacificRegion.

Part1describestheprogress intheRegiononsurveillanceofAMRandthegaps inlaboratory capacity and methodologies. Part two highlights the need to monitorantimicrobial use through common methodologies and indicators, in addition tosurveillance of AMR, to inform important policy changes to contain AMR. ThehealthsystemsresponsetoAMRalsovariesacrosstheRegion.Partthreehighlightsthe urgent need to strengthen regulation of pharmaceutical systems, antimicrobialstewardshipandinfectionpreventionandcontrol(IPC)tocontainAMRintheRegion.


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Surveillance ofAntimicrobialResistance


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Surveillance of Antimicrobial resistance (AMR) is important to contain AMR atlocal, national, regional andglobal levels.TheWesternPacificRegionhas ahistoryofdiscussions,recommendationsandactionsrelatedtoAMRsurveillancefrom1982onwards.

The WHO Regional Office for the Western Pacific was the first regional office toimplement recommendations on the surveillance of AMR in 1982 at the WHOConsultation Group for Surveillance of Antimicrobial Resistance. (1) In 2011, theRegionalCommitteeresolutionWPR/RC62.R3/2011onantimicrobialresistanceagainurgedMemberStatestomakeAMRapriority,alongwiththeWHOsix-pointpolicypackageonAMR. (2)

The WHO Global Strategy for Containment of Antimicrobial Resistance identified twofundamental priorities in efforts to combat AMR: 1) national commitment to thecontainment of AMR as a public health priority; and 2) surveillance to generatethe data required to support the development, implementation and evaluation ofresistance-containment efforts, and antimicrobial prescribing guidelines at the local,nationalandregionallevels.

AMRsurveillancetracksevolvingmicrobialpopulations,permitstheearlydetectionofresistantstrainsofpublichealthimportance,assistsinthedevelopmentoftherapyguidelines, and supports the prompt notification, investigation and containment ofnewthreats.Surveillancefindingsareneededtoinformclinicaltherapydecisionsandtoguidepolicyrecommendationsandassesstheimpactofinterventions.

A regional technical consultation on AMR surveillance in Manila in August 2013brought togethernationaland regional experts inAMRsurveillanceand laboratoryqualityassurance inboth thehumanandanimal sectors.Participantsdiscussed thedesign and implementationof regional surveillanceplans, andproposedobjectives,scope, datamanagement, quality assurance, data interpretation, dissemination anduseofsurveillancedatatoinformprescribingbehaviours.Participantsrecognizedtheexistenceofstrong,long-standingnationalandregionalactivitiesinAMRsurveillanceand external quality assurance (EQA) in manyMember States of the Region, andviewedtheseasavaluablebaseonwhichtocoordinate,integrateandbuildon.

ThegrouprecommendedtheformationofaregionaltechnicalworkinggrouponAMR(TWG-AMR), whichmet in December 2013. The TWG-AMR refined the proposalswithin the context of a broader strategic and operational framework for advancingefforts to combat AMR and to initiate discussions with Member States and otherpartnersfortheestablishmentofasurveillancenetworkfortheRegion.

TheTWG-AMRrecognizestheimportanceoflocal,nationalandregionalactions,andhasidentifiedthefollowingAMRsurveillancepriorities:

•enhance core laboratory testing capacities at local and national levels;•strengthensubnationalandnationalAMRsurveillancenetworks;•establish, in a stepwise and feasible manner, surveillance activities in WHO MemberStatesthatlackthese;

1. Surveillance of antimicrobial resistance


ANTIMICROBIAL RESISTANCE IN THE WESTERN PACIFIC REGION

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•promote and support the use of standards and methods for collection of epidemiologicalandantibioticsusceptibilitytesting(AST)dataanddatasharing,in linewiththeeffortstocoordinateandharmonizeAMRsurveillanceatthegloballevel;•encourage thedevelopment of local andnational data systems that allow for the linking ofmicrobiologyAMR surveillance data with clinical and pharmaceutical data,tosupportlocaldecision-makingforthepreventionandcontrolofAMR;and•ultimatelyestablishandcoordinatearegionalAMRsurveillanceinitiativebasedon collaborationwith existing programmeswith the proposed nameWestern Pacific RegionalAntimicrobialResistanceSurveillance(WePARS).Thisinitiativewouldbe linked to a similar network coordinating the monitoring of antimicrobial use.

Figure 1. The interface between AMR surveillance and antimicrobial use data along with clinical and demographic information to inform local, national and regional levels

Regional feedback to countries and identify

problems requiring regional collaborative actions

Inform national policies on use of antimicrobials and

identify other actions needed to contain AMR

Inform local actions for AMR containment

Regional AMRsurveillance

network(WePARS)

Regionalmonitoring ofantimicrobialuse network

National AMRsurveillance

network

Nationalmonitoring ofantimicrobialuse network

Laboratory andepidemiological

AMRsurveillance data

Antimicrobialuse data

Clinical anddemographic

data

Health-careinstitution

Source: WHO


SURVEILLANCE OF ANTIMICROBIAL RESISTANCE

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1.1 AMR SURVEILLANCE AND EXTERNAL QUALITY ASSURANCEThroughthelong-standingeffortsofnationalandregionalbodies,thereareanumberofactive,well-establishednationalandregionalinitiativesforAMRsurveillanceintheWesternPacificRegion.

Several of these initiatives are pathogen or disease specific, such as those forHIV/AIDS, tuberculosis (TB), malaria, gonorrhoea and foodborne infections.Surveillance is often integrated into vertical disease control programmes, andsample processing and laboratory testing are typically organized by nationalreference laboratories. The findings are critical for establishing and revisingnationaltreatmentguidelinesandcontrolstrategies.

Others programmes focus more broadly on common bacterial pathogens notassociatedwith specificdisease control programmes, such as those causingurinarytract infections, health-care-associated infections and sepsis. Laboratory testing isgenerallyperformedbycommunityandhospital laboratories inprimary, secondaryand tertiary care centres.

CorecomponentsofanyAMRsurveillanceactivityare:1)coordinationacross local,national and regional levels with defined allocation of resources for surveillanceactivities anddefinedprotocols; 2) an epidemiological structurewith the necessaryexpertisefordesigningsurveillancemethods;3)arobuststrategytoassurelaboratorycapacitytotestforAMRatlocalandstatelevels,includingpromotionofstandardizedAMR susceptibility testing; and 4) a platform for timely dissemination of data tointerestedpartiesandlocalandnationallevels,includingpublichealthofficials,healthworkersandresearchers.

1.1.1 Examples of disease and pathogen specific surveillance programsAntibacterial resistance

Tuberculosis – Mycobacterium tuberculosisSince the launch of the Global Project on Anti-tuberculosis Drug ResistanceSurveillancein1994,dataondrugresistancehavebeencollectedandanalysedwiththeactiveengagementofWHOcollaboratingcentres,supranationalreferencelaboratoriesand other partners. Data collection was later integrated into WHO’s annual TBsurveillanceweb-based reporting system since 2010. Data from 136 countries havebeenanalysedandpublishedintheGlobal Tuberculosis Report 2013. (3)

Gonorrhoea – Neisseria gonorrhoeaeTheWestern Pacific Region has nearly 42 million cases of gonorrhoea per annum,which is roughly 40%of theglobal gonococcaldiseaseburden.WHO’sGonococcalAntimicrobialSurveillanceProgramme(GASP)isaglobalnetwork,basedinAustralia,withparticipationof64countries.GASPreportsfromtheWesternPacificRegionarepublishedannuallyinthejournalCommunicable Diseases Intelligence. (4)

Leprosy – Mycobacterium lepraeMultidrugtherapyhasbeensuccessfullyusedtotreatleprosyforthreedecades,andrifampicinremainsthekeycomponent.Resistancetorifampicincanoccurrelativelyeasilyifitisusedasmonotherapy.Withtherecentdevelopmentofsuitablemolecular



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methods,surveillanceofresistancehasbeenmadefeasible.Anetworkofsentinelsiteswasestablishedin2007tomonitorlevelsofresistance,andmeetingshavebeenheldannuallytosharedata,technicaldevelopmentsandtrendsinnewdrugdevelopmentsforleprosycontrol.

Foodborne infections – Salmonella, Campylobacter and Shigella spp.Recognizing the morbidity and mortality associated with foodborne pathogens,theglobalmovementoffoodanimalsandproducts,andgrowingconcernaboutthehumanpublichealthimpactofantimicrobialuseinfoodanimals,WHO,theDanishTechnicalUniversity,andotherpartnersestablishedtheGlobalFoodborneInfectionsNetwork(GFN).(5)GFNisacapacity-buildingprogrammethatpromotesintegrated,foodborne laboratory-based surveillance and intersectoral collaboration amonghuman health, veterinary and food-related disciplines, in coordination with theWHOAdvisoryGrouponIntegratedSurveillanceofAntimicrobialResistance(WHOAGISAR).(6)GFNisapartofWHO’seffortstostrengthenMemberStatecapacitiesinthesurveillanceandcontrolofmajorfoodbornediseasesandtocontributetotheglobaleffortofcontainingAMRinfoodbornepathogens.

Antiviral resistance

HIVWHOhasbrought togetherorganizationsandexpertsworking in theareaofHIVdrugresistancetoformWHOHIVResNet,aglobalnetworkadvisingWHOonthecontrol and surveillance of HIV drug resistance. (7) WHO HIVResNet includes organizationsthatimplementactivitiestocontrolandmonitortheemergenceofHIVdrugresistanceincountries,individualexpertsworkinginthisarea,andanetworkofdesignatedlaboratoriesthatperformquality-assuredgenotypingtosupportHIVdrug-resistancesurveys.

Influenza – influenza virusGlobalinfluenzavirologicalsurveillancehasbeenconductedthroughWHO’sGlobalInfluenza Surveillance and Response System (GISRS) for over half a century. Itmonitorstheevolutionof influenzavirusesandprovidesrecommendations inareassuchas laboratorydiagnostics,vaccines,antiviralsusceptibilityandriskassessment.TheWHOexpertworkinggrouponsurveillanceofinfluenzaantiviralsusceptibility(AVWG)was formed in 2011 to support GISRS, and includes representatives fromWHOcollaboratingcentresforreferenceandresearchoninfluenza,nationalinfluenzacentresandpublichealthinstitutes.TheworkoftheAVWGprovidedthebasisforthedevelopmentoftheWHOguidelinesdedicatedtoantiviralsusceptibilitymonitoringforinfluenza.(8)

Antiparasitic resistance

Malaria – Plasmodium spp.Since2000,WHOhasmaintainedaglobaldatabasethatsummarizesthefindingsfrommorethan4000studies,withefficacydatathatmeetstandardcriteriaandquality.(9) TheWHOstandardprotocol for theassessmentof therapeuticefficacy is theglobal “gold standard” to monitor drug efficacy and update drug policy. This has beenadopted by all countries andmost research institutes. It is designed for all drugs,includingartemisinin-combinationtherapies.(9)

Helminthiasis – intestinal helminths and schistosomesAntihelminthics are extremely effective in treating worm infections but do notnormallykill100%oftheworms.Aconsiderableincreaseinthenumberofindividualstreated with preventive chemotherapy is expected in the next few years, with



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increasing development of anthelminthic resistance, as recognized in the Reportof theWHO Informal Consultation onMonitoring of Drug Efficacy in the Controlof Schistosomiasis and Intestinal Helminths. (10) A working group established byWHO has developed a standard protocol for evaluating drug efficacy, updated inthe 2013WHO publicationAssessing the Efficacy ofAnthelminthic DrugsAgainstSchistosomiasisandSoil-transmittedHelminthiasis.(11)

Insecticide resistanceInsecticide resistance,particularly resistance topyrethroids, threatens tounderminetheprogressmade inmalaria control in thepast decade. In response to this threat,WHO’sGlobalMalariaProgramme launched itsGlobal Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM) inMay 2012. (12)WHOhas also launchedrevised testing guidelines for insecticide resistance. (13) Countries have beenencouraged to strengthen entomological capacities at the national and subnationallevels.TheAsia-PacificNetwork forVectorResistancehasbeen established for thispurpose.

1.1.2 Regional programs for surveillance of resistance in common bacterial pathogensThere are a number ofWHO-coordinated andWHO-affiliated regional and globalcollaborations for pathogen-/disease-specific surveillance, as described above.However,thereisatpresentnosuchWHOprogrammeintheWesternPacificRegionformonitoringresistanceinbacterialpathogensthatcausecommoncommunity-andhealth-care-associatedinfections,suchasurinarytractinfections,respiratoryinfectionsandsepsis.ThoughthereisnoregionalWHOprogrammeatpresent,manycountriesintheRegionhadestablishednationalAMRsurveillancenetworksover25yearsago,withmanymoreinitiatingactivitiessincethen.(14)AshortsummaryofsurveillancenetworksintheRegionisprovidedinTable1.

Further details about their organization, history and accomplishments will beavailable in thedraftAMR Surveillance Networks in the Western Pacific Region (draftdocument, 2014). Inaddition to thesenetworks,mostMemberStatesareactive incollectingresistancedata,eitherthroughongoinginstitution-levelsurveillanceoradhoctargetedsurveysonpriorityissues,notablyinthelesspopulousMemberStatesoftheRegion.

CoreelementsofWHO’sstrategyfortheregionalAMRsurveillanceprogrammemustincludestrengtheningnationalprogrammes,integratingtheseactivitiesintoaregionalcollaboration,andlinkingAMRsurveillancefindingstoactionthroughcoordinationwithpolicy-makersandnationalauthoritiesforalocal,nationalandregionalresponse.



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Table 1. National and regional networks for AMR surveillance in the Western Pacific Region

Country or areas Programme name Contact organizationAsia Region Asian Network for Surveillance Samsung Medical Center of Resistant Pathogens (ANSORP) Australia Australian Group on Australian Group on Antimicrobial Antimicrobial Resistance (AGAR) Resistance, Royal Perth HospitalCambodia* NAMRU-2 U.S. Naval Medical Research Unit-2China Ministry of Health National Antimicrobial Ministry of Health, Zhejiang University

Resistant Investigation Net (MOHNARIN) China CHINET Hua Shan Hospital, Shanghai Medical

University, Institute of AntibioticsChina, Hong Kong (SAR) Hong Kong Antibiotic Hong Kong Hospital Authority,

Stewardship Program (ASP) Centre for Health ProtectionFederated States Federated States of Micronesia FSM Department of Health and Social Affairs

of Micronesia* Surveillance NetworkJapan Japan Nosocomial Infections National Institute of Infectious Diseases Surveillance (JANIS) Malaysia National Surveillance of Institute for Medical Research

Antimicrobial Resistance Programme (NSAR) Mongolia National Laboratory Network National Center for Communicable Diseases,

Health Sciences University of MongoliaNew Zealand ESR Antibiotic Reference Laboratory Institute of Environmental Science

and Research Ltd (ESR)Philippines Antimicrobial Resistance Research Institute for Tropical Medicine

Surveillance Program (ARSP) Republic of Korea Korea Antimicrobial Resistance Korea National Institute of Health,

Surveillance Program (KARMS) Center for Infectious DiseasesRepublic of Korea Korean Nationwide Surveillance Yonsei University College of Medicine

of Antimicrobial Resistance (KONSAR) Republic of Korea Korean Network for Studies on Samsung Medical Center

Infectious Diseases (KONSID) Singapore The Network for Antimicrobial Tan Tock Seng Hospital

Resistance Surveillance (NARS-Singapore) Viet Nam Viet Nam Resistance Project (VINARES) National Hospital for Tropical Diseases

Source: Information adapted from Shaban RZ, Cruickshank M, Christiansen K and the Antimicrobial Resistance Standing Committee. National surveillance and reporting of antimicrobial resistance and antibiotic usage for human health in Australia. Canberra: Antimicrobial Resistance Standing Committee, Australian Heath Protection Principal Committee; 2013.

*Additional surveillance networks identified from unpublished WHO Regional Office for the Western Pacific AMR surveillance networks survey conducted in July 2014.



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1.1.3 Regional external quality assuranceA survey of regional (non-national) programmes that provide EQAwas conductedin 2014. The survey showed that institutions inmostMember States participate inone ormoreprogrammes. Programmes that had a general bacteriology componentincludedthefollowing(numbersinparenthesesindicatethenumberofWesternPacificcountriesandareasincludedintheprogramme):

•CollegeofAmericanPathologists,UnitedStatesofAmerica(notavailable);•HongKongInstituteofMedicallaboratorySciences,HongKongSAR(China);(2);•PacificParamedicalTrainingCentre(PPTC)RegionalExternalQualityAssurance Programme(REQAP),NewZealand(16,notablyPacificislands);•RoyalCollegeofPathologistsofAustralasia(RCPA)QualityAssuranceProgrammes (RCPAQAS),Australia;(11);and•UnitedKingdomNationalExternalQualityAssuranceScheme(UKNEQAS),United KingdomofGreatBritainandNorthernIreland(6).

The following targeted pathogen- and disease-specific EQAprogrammeswere alsoidentified:•GonococcalAntimicrobialSusceptibilityProgramme(GASP)(15);•GlobalFoodborneInfectionsNetwork(GFNEQAS)(15);•HIVResNet(3);•NationalReferenceLaboratory,Australia(17);and•Tuberculosis(29).

AnumberoftheaboveprogrammesarecoordinatedbyWHOorbydesignatedWHOcollaboratingcentres.Mostoftheothersarecommercialventures,butseveralhavehadpreviousformalcollaborationswithWHOandmostexpressastrongwillingnesstocollaboratewithWHOinpromotingEQAintheRegion.

A similar survey for national EQA programmes in theWestern Pacific Regionwasconducted in July 2014 to identify the major challenges in quality assurance andlaboratorycapacitytotestforAMRwithincountriesoftheRegion.

1.2 PROPOSED REGIONAL AMR SURVEILLANCE SYSTEMNationalAMRsurveillancesystemscanprovidedatatobeincorporatedintoaregionaldatabasethatwillgenerateinformationtosupportactiontocombatAMR,inparticular,antibioticresistanceatnationalandregionallevels.ThesurveillancesystemwillalsoaimtogiveAMRitsduerecognitionandattentioninMemberStatesasapublichealththreatthatneedstobetackledeffectivelyatthenational,regionalandgloballevels.

The proposed name of the regionalAMR surveillance system that will eventuallycoordinateanddisseminatenationalAMRdataataregionallevelistheWesternPacificAntimicrobialResistanceSurveillance(WePARS).

1.2.1 Goal The overall goal is to strengthen national network and establish a regional AMRsurveillancedata-sharing system toprovide information for combatingAMR in theRegion.



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1.2.2 ObjectivesTheobjectivesare:(1) togenerateAMRdatatopermitongoingtrackingofmicrobialpopulationsatthe local,nationalandregionallevels;(2) tosupportthedevelopmentandevaluationofcontainmentstrategiesand ultimatelytoreducemortality,morbidityandcostsofAMRintheRegion,in partnershipwithpolicy-makersandotherstakeholders;(3) toenhanceearlydetectionmechanismssothattimelyalertsareprovidedforthe controlofemergingthreats,includingoutbreaks;(4) tostrengthenlaboratoryandepidemiologicalcapacityforgenerating,interpreting

andusingAMRsurveillancetoguideandregularlyupdateprescribingguidelines,infectioncontrolinterventionsandpublichealthpolicy;and

(5) to contribute nationalAMR data to a regional and a globalAMR surveillancesystem.

1.2.3 ScopeThefocusofthisnewinitiativeis thesurveillanceofAMRinbacteria inthehumanhealth sector, not covered by existing pathogen- and disease-specific programmes.AMRsurveillanceinthefoodandanimalhusbandrysectorwillalsobeincluded.AMRsurveillance in the Region will generate and collate information to monitor AMRtrends, track changes inmicrobial populations, provide early detection of resistantstrainsthatareofpublichealthimportance,promptlynotifyandcontroloutbreaksduetoantimicrobial-resistantmicroorganisms,andinformlocalandnationalcontainmentstrategiesandprescribingguidelines.

Findings from this surveillance effort, alongwith those of the disease- and pathogen-specificprogrammesaswellasparallelprogrammesformonitoringantimicrobialuseandhealth-care-associatedinfectionswillbeintegratedbylocal,nationalandregionaladvisorygroupsanddecision-makerstosupportintegratedresistance-containmentstrategies.

1.2.4 Critical elementsThe following elements, elaborated in subsequent chapters, will be critical to thesuccessofWePARS:•networkedmodelforregionalAMRsurveillance•nationalAMRsurveillancestrategies–potentialmodels• informationmanagementandreporting•qualityassurancestrategy•networkgovernanceanddataownership•surveillancetosupportcontainmentofAMR.

1.2.5 Resource mobilizationTheproposedWePARSsurveillancesystemwillrelyonthemobilizationofhumanandmaterialresourcesforsuccessandsustainability.

The core of theWePARS data collection strategy and recommendation to nationalAMRsurveillancewillbecollectionofcoreepidemiological(patient)informationandroutinemicrobiologicalfindings fromclinicalsamplescollectedandprocesseddaily



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throughout theRegion.With the exceptionof targeted surveyprotocols, fundswillgenerallynotbeneededtosupportsamplecollectionandtesting.However,resourcesandtoolswillbecriticalfor:• assuringthequalityoftestperformancebyclinicallaboratoriesthroughinternaland externalqualityassurance,reagentsofsufficientquality,sitevisitsandeducational opportunities;• informationmanagement,dataanalysisandinterpretation;•reportpreparation,interpretationanddissemination;•network organization, including meetings with participating institutions; and•coordinatedactionwithlocal,nationalandregionalstakeholders.

Participating surveillance sites and network coordinating institutions typicallycoverthesecosts.Inseveralinitiatives,ministriesofhealth,WHO,nongovernmentalorganizations,clinicalsocieties,researchagenciesandindustrypartnershaveprovidedadditionalsupport.

Mostnetworksmustfocusonfundraisingtomaintaincoreelementsofthesurveillanceprogramme (data generation, collection, analysis, report generation and qualityassurance). This can be a significant challenge. Unfortunately, the potential impactofsurveillanceisoftenlimitedbyinsufficientresourcestotranslateinformationintoaction, including advocacy, education, and regulation and policy development. Tomaximize thevalueof resources and identifypriorities, an initialneedsassessmentshouldbeconducted.

1.2.6 Networked model for regional AMR surveillanceWePARSwill be a network of national and subnational networks, building on theactivities and accomplishments ofWestern Pacific RegionMember States. The coreoftheseeffortsisthecollection,processingandtestingofpatientsamplessubmittedtomicrobiology laboratories (alongwith core clinical/epidemiological information)throughouttheRegion,coupledwiththeirinterpretation,sharingandtranslationintoactionatthelocal,nationalandregionallevels.

Criticalelementsofthisnetworkedmodelinclude:•surveillancesites•surveillancenetworkcoordination•referencelaboratories• integrationintheWesternPacificRegion•collaboratorsandstakeholders.

Surveillance sitesAn AMR surveillance system is based on data generated by surveillance sites,including themicrobiology laboratory, complementedby corepatientdemographic,epidemiologicalandclinicalinformation.

Surveillance network coordinators should strive for wide geographical anddemographic representation. To investigate the public health impact of AMR inbacteriafromanimaloriginonhumanpopulations,coordinatorsshouldalsoconsidertheinclusionoffood,animalandenvironmentalsurveillancesites.

Toensuredataquality,participatinglaboratoriesmustfollowstandardizedprotocolsandparticipateinEQAprogrammes.Additionalcriteriaforselectionincludelaboratoryandepidemiologycapabilityand,mostimportantly,theenthusiasmofpersonneltoparticipateinthenationalprogramme.ThereisalsoaneedtostrengthencapacityforepidemiologicalanalysesandAMRtestinginMemberStateswhereitislackingorirregular.



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It is important to identify human resources to conduct surveillance activitiesand provide education for all participants in the surveillance system, includinglaboratories,epidemiologistsandclinicianswhohandleandanalysepatientdata.

Coordination of regional surveillance networkThe role of network coordinators is critical in establishing and sustaining thesurveillanceinitiative.Inpartnershipwithnetworkmembersandotherstakeholders,coordinators establish the scope, priorities and activities of the programme, setstandards and protocols for participation, ensure sufficient human and financialresources to accomplish the work, and work with external partners in tyingsurveillancefindingstopolicyandaction.

Responsibility for the collection, management, analysis and interpretation of datasubmittedbyparticipatingsitesresidesprimarilywiththenetworkcoordinators;thus,thecoordinatingteamshouldincludepeoplewithexpertiseinmicrobiology,infectiousdiseases,epidemiologyandinformationmanagement.

AMR surveillance coordinators should collaborate regularly with nationalmultisectoral groups responsible for establishing and assessing strategiesand interventions for containment of resistance. AMR surveillance activitiesshould incorporate experts in antimicrobial use, veterinary sciences and mediacommunications,amongothers,foracomprehensiveapproachtocontainingAMR.

1.2.7 Role of reference laboratories in regional surveillance networkInasurveillancenetwork,thefunctionsofreferencelaboratoriesinclude:confirmationofunlikelyorimportantresistancephenotypes;molecularcharacterizationofresistantstrains; and maintenance of an isolate strain bank. Reference laboratories oftencoordinate EQA schemes, training activities and laboratory site visits. Ideally, thereferencelaboratoryideallyshouldbeinthesamecountryasthesurveillancenetwork.Ifthisisnotfeasible,collaborationwithexternalpartnerswillbeneeded.

Staff should have a high degree of expertise in microbiological testing, datamanagement and epidemiologicalmethods, andmaintain up-to-date knowledge ofemergingresistanceproblemsanddiagnosticissues.

1.2.8 Regional consolidation of AMR surveillance dataTheWHORegionalOfficefortheWesternPacificcanplayakeyroleinconsolidatingsurveillancefindingsfromnationalsurveillanceprogrammesintoaregionalpictureofemergingtrends;mentoringandstrengtheningnationalprogrammes;providingEQAfortheAMRnetwork;andprovidingtools,ensuringstandardizedmethods,protocolsandguidelinestoMemberStates.

TheRegionalOfficeshouldestablishacentralizeddatabasefortheRegion,preferablyonline, to receive structured data from participating sites, and provide tools andeducation for the generation of suchdata. The centralizeddata-processing locationshouldberesourcedtoundertakeanalysis, interpretationandreporting.Thesystemshouldhavetheabilitytolinkwithdatafromothersystems,suchastheWHOglobalsurveillance system being developed and those monitoring antimicrobial use andAMRinanimalandfoodsources.



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The Regional Office is the key advocate for advancing resistance-containmentinitiatives in partnershipwithministries of health, nongovernmental organizationsandprofessionalsocieties.Collaborationamongpartnerswillultimatelysupportthedevelopmentofguidelinesandinterventionsatlocal,nationalandregionallevels.

Collaborators and stakeholdersTheWHO Global Strategy for Containment of Antimicrobial Resistancerecommendsestablishment of intersectoral task forces with broadmembership for coordinatingsurveillanceactivitiesandoverseeingpolicyinterventionsandadvocacyefforts.Thesetaskforcesshouldcompriserepresentativesfromauthoritiesresponsiblefornationalpolicy,drugregulationandprocurement;healthfinancinggroups;clinicalprofessionalsocieties; veterinary and food-production services; pharmaceutical and diagnosticindustry; patient advocacy groups and the publicmedia.At the regional level, theWorldOrganisationforAnimalHealth(OIE),‘FoodandAgricultureOrganizationoftheUnitedNations(FAO),AssociationofSoutheastAsianNations(ASEAN)andAsia-PacificEconomicCooperation(APEC)shouldbeinvolved.

1.2.9 National AMR surveillance strategies – potential modelsResistant microorganisms present a diverse set of clinical, technical andepidemiological challenges. Consequently, a single surveillance initiative willgenerally not have the expertise, time and resources to address all the desiredtherapeutic,diseasecontrol,policyandresearchissues.Thus,inestablishingaplanforAMRsurveillance,surveillancecoordinatorsshouldidentifycriticalinformationneeds,understand the richness and limitations of AMR surveillance data resources, andprioritizegapswhereadditionalactivitiesarerequired.

ArationalapproachtonationalAMRsurveillanceshould:1. maximize the use of information generated in the course of routine diagnostic

samplingandtestingwithanunderstandingofboththevalueandlimitationsofthisdatasource;and

2. integratecomplementaryadditionalprotocolswhereroutinedataareinsufficientinquantity,qualityormicrobiologicalorepidemiologicaldetail.

ThefollowingsectionsdiscussoptionsfornationalAMRsurveillanceplansdependentprimarilyoncountries’resourcesetting(low,middle,high)andlaboratorycapacitytotestforAMR.

Alert organism surveillanceIn the course of routine diagnosticwork, laboratory staff occasionally come acrossstrainswithunlikely,unexpectedorimportantfindingsofpublichealthsignificance.Phenotypesmaybe identifiedas“unusual”on thebasisof their rarityworldwide–vancomycin-resistantStaphylococcus aureus,fluoroquinolone-resistantSalmonella typhi,oronthebasisofthelocalornationalexperience–vancomycin-resistantEnterococcus,cefotaxime-resistantEscherichia coli.

As the noteworthy finding may be due to a laboratory error, laboratoriesshould have mechanisms for the prompt recognition, local confirmation and, ifappropriate,nationalorinternationalconfirmation,notificationandinvestigation.Thesuccessofanalertorganismsurveillancesystemdependsontheattentionofinformed microbiologists performing ongoing review for important or unlikelyresults, and procedures for confirmation at the national level. Many countriesmaintain a list of such “reportable”/“alert” organisms for which nationalconfirmationisrequired.



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While the intent of alert organism surveillance is prompt recognition and responsetoinfectionsofpublichealthimportance,animportantancillarybenefitisimprovedlaboratory capacity through the recognition, investigation and resolution ofdeficienciesinlaboratoryperformanceand/ortestreagentquality.

Routine surveillanceClinical specimens collected from patients are sent to laboratories and processed bymicrobiology laboratories worldwide. By capturing, organizing and analysing theclinicalinformationandsampleresults,investigatorscanidentifynewthreats,recognizeand track strain subpopulations, identify outbreaks, monitor resistance trends andinvestigatemultidrugresistancefortheevaluationoftherapeuticalternatives.

Allofthisispossibleandpaidforthroughroutinepracticesforclinicalsamplingandprocessing. Through investments in information capture, sharing, management,analysis and interpretation, and the accumulated data generated by clinicians andmicrobiologylaboratories,itispossibletoobserveandrespondtochangingmicrobialthreats.

This approach has a number of advantages – low cost with excellent long-termsustainability and based on clinical populations. A broad range of patient-,syndrome- and organism-resistance issues can be investigated both prospectivelyandretrospectively,encompassingwidegeographicalanddemographiccoverage.Inmostcountries, this typeofmonitoringiscomprehensive,andincludesresultsfromall routinely available microbial species, specimen types and antimicrobials tested,thoughitisalsopossibletochooseasubsetofpriorityspeciesandsampletypes.

Withadvancesininformationtechnology,alertnotificationsarepossibleinrealtimeas laboratory technologists enter or download results into surveillance informationsystems:immediatenotificationof“alert”organismsispossible,withnotificationofrelevant authorities, and recognition of statistical clusters of strain subpopulationssuggestiveofcommunityorhealth-careoutbreaks.

Anancillarybenefitofcoreroutinesurveillanceisimprovedlaboratorycapacity.Whileinternal and external quality assurance strategies focus on a laboratory’s ability toperformgood-qualitytesting,systematicreviewsofisolate-basedtestresultsprovideamuchmorethoroughinsightintothelaboratory’sroutinepractices.

Ontheotherhand,routinesurveillanceusuallydependsontheclinicalsamplessenttolaboratoriesfordiagnosisandAST.Thismeansthatthemajorityofsamplescomefrompatientswithsevereinfections(particularlyhealth-care-associatedinfectionsandthoseforwhichfirst-linetreatmentfailed),sothatcommunity-acquiredinfectionsareunderrepresented.Thisimbalanceislikelytoresultinhigherreportedresistanceratesthanwouldbefoundforthesamebacteriaincommunityorpopulation-basedsamples,aswasshowninsomereportswithdatasubmittedseparatelyforthesepatientgroups.Non-representativeness andbiased sampling aremajorpitfalls in the interpretationand comparison of results. Treatment guided by limited and biased informationmay risk driving empirical therapy unnecessarily towards more broad-spectrumantibacterialmedicines.ThiswillincreasetheeconomicimpactofAMRandacceleratetheemergenceofresistanceresultingintheuseoflast-resortantimicrobials.Toaddresstheselimitations,investmentshouldbemadetoimprovethedesignofthesurveillancesothatmicrobiologicaldatacanbelinkedtoclinicalandepidemiologicaldata.

Targeted surveillance and surveysAs mentioned above, routine surveillance may not generate sufficient informationon thescopeandextentof theAMRproblemtoguidepreventionandcontainment



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policies, advocacy or research needs. Problems may lie in the volume of orepidemiological biases in routine samples, or lack of sufficient patient and clinicaldetails to assess the effectiveness of interventions, risk factors, the clinical andeconomicimpactofresistance,orinsufficientmicrobiologicaldetailtoguidevaccineselection,orcharacterizetheclonalityofsuspectedoutbreak-relatedstrains.

In targeted surveillance (ongoing) or survey (one-time or periodic) initiatives,programmecoordinatorshavetheflexibilitytodevelopprotocolsthattargetspecificobjectives and improve data collection in specimen collection, patient clinical andepidemiological details, and microbiological testing. A well-designed targetedsurveillanceprogrammeprovidesanopportunitytoelicitspecificresponsestopriorityquestions of clinical, epidemiological or scientific importance – establish standardtreatment guidelines (STGs); evaluate risk factors for resistance, transmission andcontrolstrategies,morbidityandmortality;andconductmolecularcharacterizationofclonalpopulations.

LinkageofAMRsurveillance todiseasesurveillance in targetedsurveys isvaluableand may permit incidence measurements and evaluation of the impact of controlinterventionsindisease-specificcontrolprogrammes.Examplesofdiseasesurveillanceinclude TB and malaria. Periodic short-term studies for selected populations anddiseasescanbeaviableoptionifcapacityisinplace,permittingestimatesofdiseaseburdenandimprovingtheepidemiologicalrelevanceofAMRsurveillanceactivities.Targetedsurveillanceandsurveyprotocolshavesomeimportantlimitations:1)theyare generally resource and labour intensive; and 2) they typically address priorityorganismsorissuesofclinicalorpublichealthimportanceinrelativelysmallnumbersofpatientsandisolates.Thenarrowfocusofspecialprotocols limits theirutilityforidentifyingnewthreatsandtrackingstrainpopulations.

1.2.10 Collection, analysis and reporting of AMR surveillance dataAMRsurveillancerequiresarobustpracticalstrategyfortimelymanagementofdatasubmittedbyparticipatingsites.Steps tobeconsideredaredatacollection,analysisand interpretation, as well as reporting. Fortunately, due to ongoing advances ininformation technologyaswellas improvingexpertise in informaticswithinhealth-care facilities (HCFs), much more is possible today than ever before to supportcomprehensivereal-timeapproachestodatacapture,analysis,alertsandactionsatthelocal,nationalandregionallevels.

MemberStateshave the responsibility tomonitorAMRsurveillanceat thenationallevelandshare thedataat the regional level fora collective response tocontainingAMR. For AMR surveillance networks to participate in the WePARS network,participantsmustalsoagreeonissuesofdataownership,confidentialityanduse.

Isolate-level data collectionPatient and isolate-level data provide the richest insights into the evolvingepidemiologyofmicrobialandresistance threats.Corepatient information toguidelaboratorytestingandinterpretationofresultsshouldaccompanythepatientsampletothelaboratoryandbeenteredinthesamedatasetastheASTresult.ForASTresults,ideallyquantitativesusceptibilitytestresults,suchasdiskdiffusionzonediametersorminimuminhibitoryconcentration(MIC)values,shouldbeentered.

Laboratories at the local, national and regional levels in over 110 countries usedWHONET for thispurpose. (15)WHONET is available for freedownload from theWHOwebsite(http://www.who.int/drugresistance/whonetsoftware/).Resultsmaybeenteredmanuallyorconvertedfromlaboratoryinformationsystems,instruments



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ordesktopsoftwarewithBacLink(partoftheWHONETpackage)forthepurposesofdataanalysisandsharing.Analternateapproach,insettingsfacingadministrativeortechnicalbarriers,istofocuson specific clinical entities/syndromes (e.g. sepsis), organisms (e.g. Staphylococcus aureus and Escherichia coli)andspecimentypes(e.g.blood).

Regardlessoftheapproach,duplicatefindingsfromthesamepatientduringthesamediseaseepisodeshouldbeeliminated.

Aggregate data collectionAn alternate approach to collecting routine findings is for network coordinatorsto request specific, predefined aggregate statistics and metrics; for example, theproportion of outpatient blood samples positive for Escherichia coli resistant toimipenem or meropenem, or from urinary isolates resistant to co-trimoxazole orfluoroquinolones.Onemaytargetspecificantimicrobial–microorganismcombinationsor alternatively collect statistics on all clinically relevant antimicrobials to permit acomparisonoftherapyalternativesandtracktheirrelativetrendsovertime.Datamaybeaggregatedattheleveloffacilities,provinces,hospitaltypeornationally.Furtherguidance is presently being prepared by working groups coordinated by WHOheadquarters.

Collectionofaggregatestatisticsissimplefromadata-sharingperspective,butthereis littleabilitytoevaluatedataqualityor investigate issuesinmoredepththanthatprovidedby thepatientdata and resistanceproportions collected.This approach isgenerallynotrecommendedunlessbarrierspreventthemorecomprehensiveisolate-basedapproach.

1.2.11 Surveillance network feedback to data contributorsNoteworthymicrobiologytest-resultfindingsduringthefirstyearortwoofoperationcanoftenbeexplainedbylaboratorytestingerrors,interpretationsorepidemiologicalbiases.Surveillancecollaborationsshouldthusbeviewedinthecontextofaprocessof continuousquality improvement.Directed laboratory feedback isanopportunitytoaddresstheproblemsidentifiedandeducatemicrobiologystaff,therebyimprovingthequalityofsurveillancefindings,andtheabilityoflaboratoriestoprovidereliablediagnosticsupporttohealth-careproviders.

Absent or too limited patient data also compromises adequate analysis, and thusshouldbefedbacktoclinicianstoimprovesamplingroutinesandinformation.

Network coordinators must provide appropriate, timely feedback and guidancetoparticipatingfacilities,forexample, intheformofindividualletterstolaboratoryand hospital directors detailing some of the questionable or unlikely results in thesubmitted dataset. In addition to commentary on the quality of susceptibility testresultsperformed,feedbackshouldalsoaddressotheraspectsoflaboratorypractices,suchastheappropriatenessoftheantimicrobialsselectedfortesting,selectivetestingpracticesthatmayinfluenceresistanceestimates,andclinicalrelevanceofreportssenttoclinicians.TheWesternPacificRegionshouldalsoprovidethistypeoffeedbacktonetworkcoordinatorssubmittingdatatotheregionalnetworkifunlikelyorunusualresultsaresubmitted.



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1.3 QUALITY ASSURANCE STRATEGIES FOR AMR SURVEILLANCEAn essential requirement of any laboratory providing microbiological services forpatient decision support, public health investigation, research and/or regulatorypurposesisarobuststrategyforensuringtheadequacyoftestpracticesandreagents,and the reliability of test results. InAMR surveillance activities, a comprehensivestrategyforensuringqualityshouldaddresstheclinicalqualityandepidemiologicalrelevance of samples collected (thus also including patient information provided),the reliability of laboratory findings, and the quality of expertise in result analysis,interpretationandcommunication.

The reliability of laboratory test practices, strategies and procedures for ensuringquality are generally well defined through standard operating procedures. Forantimicrobial susceptibility test results, there are reference bodies such as theClinicalandLaboratoryStandardsInstitute (CLSI)andtheEuropeanCommitteeonAntimicrobialSusceptibilityTesting(EUCAST).Recommendationsforqualitycontrolassuranceforantimicrobialsusceptibilitytestresultsaredescribedbelow.

Biases in sample collection are more difficult to address from a strict laboratoryperspectivebutcanbebetteraddressedifpatientsorpopulationsaredefinedandthisinformationisincludedinthedataset.Potentialbiasesinthedatamustbeconsideredwheninterpretingandapplyingfindingsonresistance.Ifresourcesareavailableforthecollectionofclinicalsamplesbeyondthosetakenforroutinecare(andlookingbeyondthesubsetofpatientsthattypicallypresentstomedicalcare),thentargetedsurveyscanascertainandquantifypotentialdatabiases.

Anumberoftoolshavebeendevelopedfortheassessmentoflaboratories.WHOhasproduced a tool that has components for assessing individual laboratories and fornationallaboratorysystems(http://www.who.int/ihr/publications/laboratory_tool/en/).Thesetoolsaregenericandaredesignedtobeadaptedtotheneedsofeachuser.AquestionnairehasalsobeendevelopedtomonitornetworksforAMRsurveillance(http://www.who.int/drugresistance/whocdscsrrmd20031.pdf?ua=1).

1.3.1 Internal quality controlLaboratories require procedures for assuring the quality of test reagents andthe adequacy of test performance. The first line of assessment for antimicrobialsusceptibilitytestresultsistheuseofstandardqualitycontrolstrains.Thetwomostcommonly used standardizedmethods for susceptibility testing are published andupdated annually by the CLSI and EUCAST. In theWestern Pacific Region, CLSIis more commonly used. Results obtained from users of either of these methodsare becoming more comparable for most (but not all) of the common pathogens,particularlyifthenon-susceptibleportionisreported.WhiletheCLSIguidelinesareavailableforpurchase,EUCASTguidelinesaredownloadableforfree.

BoththeCLSIandEUCASTguidelinesdetailstandardsforqualitycontroltestingandperformance.Inhigh-resourcesettings,manylaboratoriestestover10distinctqualitycontrol strainsdaily to ensure compliancewith official recommendations. In lower-resource settings, anumberofnationalnetworks recommendweekly testingof thestrainsbelowasaminimalleveloftesting:



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ATCC25922 Escherichia coliATCC27853 Pseudomonas aeruginosaATCC25923 Staphylococcus aureus(fordiskdiffusiontesting)ATCC29213 Staphylococcus aureus (forMICtesting)ATCC49619 Streptococcus pneumoniae.

Whileroutinetestingofqualitycontrolstrainsisimportantinassuringalaboratory’scapabilityforqualitytesting,acomplementarystrategythatexploresthelaboratory’sroutine performance is needed. This includes frequent and systematic reviews ofaccumulated results for findings suggestive of poor-quality reagents or deficienciesin test performance; for example, the frequent identification of unlikely resistancephenotypes or deformations in zone diameter or MIC distributions, which aresuggestiveoferrorsininoculumorresultreadingand/orrecording.

1.3.2 External quality assuranceParticipation in EQA schemes for the identification of organisms, susceptibilitytestingand test interpretationhasprovenvalue in identifyingandcorrectingerrorsin test performance, evaluating laboratory proficiency to participate in networkcollaborations, and updating microbiologists on emerging issues of resistance anddiagnostictechniques.

NationalprogrammesforEQAexistinmostofthelargerMemberStatesoftheRegion.They cover a number of clinical laboratory areas, such as microbiology (includingorganismidentificationandAST),bloodbankandchemistry.Asystematicoverviewofthesenationalprogrammesdoesnotyetexist,butasurveywasconductedinJuly2014andtheanalysisiscurrentlybeingundertaken.

There are severalwell-established, active regional programmes for EQA in generalbacteriology. The three most active ones are RCPAQAS, PPTC REQAP, and UKNEQAS,andallhaveexpressedtheirwillingnesstodiscusspossiblecollaborationwithWHOininitiatinganEQAprogrammeonAMRfortheRegion.

ExcellentperformanceinanEQAprogrammedoesnotnecessarilyreflectthequalityof laboratory testing on a daily basis for typical clinical specimens. To addressthis discrepancy between capability and reality, careful review by surveillancenetworkcoordinatorsofsubmitteddatafilesisrecommendedtoidentifypreviouslyunrecognizedissuesinsusceptibilitytestingand/ororganismidentification.

1.3.3 Reference laboratory confirmation and characterizationFor strains with important or unusual phenotypes identified by participatinglaboratories, there should bemechanisms for confirming the results at a centrallevel. This process can conveniently be integrated into an alert organismsurveillanceprogramme.Iftheresultsofthesendinglaboratoryareincorrect,thendirectedfeedbackwithappropriateguidanceshouldbereturnedtothelaboratory.Central confirmationof the resultspermitsmoredefinitive statements about theexistence of certain resistance phenotypes in the country. Reference laboratoriescould also provide support for capacity development in terms of training andtechnicalsupport.



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1.3.4 Capacity development for clinical microbiologyWhiletheaboverecommendationsfocusonspecifictechnicalprioritiesinlaboratorytesting relevant for AMR surveillance, a broader view of laboratory and clinicalcapacity-building isalsorequired.These includestrategies to improve“diagnosticstewardship”, i.e. drawing a sample for analysis in patient categories, dependingon the needs and the local resistance situation, implementing laboratory qualitymanagement systems to address the proper utilization of laboratory servicesby clinical staff, continuous efforts to strengthen human and material resources,procedures for ensuring the safety of laboratory staff, and proper disposal ofbiosafetyhazards.

1.4 GOVERNANCE AND OWNERSHIP OF AMR SURVEILLANCE DATA1.4.1 Network structure and coordinationForsuccessfullong-termcollaborationwithinWePARS,nationalnetworkcoordinatorsandparticipantsshouldestablishtermsofcollaborationandcriteriaforparticipation;responsibilities and expectations of network members; policies covering dataownership, security, access and use; and strategies for collaboration with externalstakeholders.

Membership in WePARS shall include subnational, national and regional AMRsurveillance networks designated by the respective ministries of health ofMember States in the Western Pacific Region. The WHO Regional Office willassess the readiness of each such network to join, considering past activities andaccomplishments, organizational and technical capacity, surveillance strategy, andwillingnessandabilitytoshareagreeddatawiththeregionalcollaboration.MemberStateshaveanationalresponsibilitytomonitorandshareAMRsurveillancedatawithotherMember States of the Region and the RegionalOffice for collective action tocontainAMRintheWesternPacificRegion.

While eachWePARS candidate network will establish its own internal criteria forinstitutionalparticipationandqualitystandards,theRegionalOfficewillreviewthesestandards and,where appropriate, recommend actions to strengthen these prior tonetworkenrolmentinWePARS.

A TWG-AMR was established in December 2013 to provide guidance for thedevelopmentofAMRcontainment strategies in theRegion thatareoutlined in thisdocument.

1.4.2 Data ownershipMember States and networks that contribute data are considered to be the ownersof theWePARSdata, andultimatelymustdirect thepolicies andpriorities fordatamanagement, analysis and use. The Regional Office is a data handler recognizedby Member States as the appropriate body to collect, interpret and disseminatesurveillancefindingstoinformpolicy-makersatthelocal,nationalandregionallevelsinaccordancewithguidelinesandprotocolsestablishedbyWePARSmembers.



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1.5 SURVEILLANCE TO SUPPORT CONTAINMENT OF AMRThe WHO Global Strategy for Containment of Antimicrobial Resistance identified asa fundamental priority the establishment of a national multisectoral task force,appropriatelyfundedandempowered,toformulate,implementandevaluatenationalplans for the containment of AMR. While surveillance is required to recognizeemergingthreatsofAMR,findingsmustbetranslatedintoactionwithinthecontextofcollaborativelocal,nationalandregionalstrategiesforcontainmentofresistance.

Information generated through both surveillance of AMR and antimicrobial useshould be made widely available to local, national and regional decision-makers.Thedatawillbeusedforpolicydevelopmentonantimicrobialuseatalllevels;earlyrecognition of and resistance to new threats, including multidrug-resistant (MDR)microbes; improved diagnostic testing for patient care and outbreak preparedness;benchmarkingof institutional andnational experiences onAMR; and assessing theimpactofdiseasecontrolandresistance-containmentinterventions.

This requires effective and sustained collaboration among national authorities;clinicians, pharmacists, epidemiologists, microbiologists, and their professionalsocieties; researchers; pharmaceutical anddiagnostic industry leaders; veterinariansandfoodproductionexperts;patientadvocacygroups;andrepresentativesofpublicmedia. The format in which the surveillance findings and recommendations arepresentedmustreflecttheinformationneedsandscopeofresponsibilityofrecipients.These include, for example, network annual reports, newsletters, policy papers,scientificpublicationsandpresentations,websites,patientbrochures,articlesinlocalnewspapers,andinterviewswithlocaltelevisionandradiorepresentatives.

Given the extensive use of antimicrobials in agriculture and aquiculture, especiallyas growth promoters in food production, it is important to address the drivers ofresistance in the animal health sector as well. Linkage of antimicrobial use andAMR surveillance programmes with ministries of agriculture and aquiculture,foodproducers,veterinarians,OIEandFAOshould thusbeviewedascrucial foracomprehensiveactionplantoaddresscontainmentofresistance.


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Monitoring of antimicrobial use


MONITORING OF ANTIMICROBIAL USE

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2. Monitoring of antimicrobial use Monitoring of antimicrobial use tracks how frequently and in what volumesantimicrobials are used. It also tracks how patients and health-care providers useantimicrobials. The goal of tracking antimicrobial use is to provide information toguidepolicyandeffectivedecision-makingontheappropriateuseofantimicrobialsin order to contain the increasing burden of resistant microorganisms. Decisionsregarding antimicrobial use should support the provision of effective antimicrobialtherapy to patients and the preserved usefulness of antimicrobials for futuregenerations.

The overuse,misuse and abuse of antimicrobials have contributed to the alarmingspreadofAMRworldwide.IntheWesternPacificRegion,thereisaglaringabsenceofresearchonthestatusofantimicrobialuseandconsumption,andlackofregionalmonitoring of antimicrobial use aswell as the volumes consumed by humans andanimals.

Antimicrobial use should be monitored at the local, national, regional and globallevels.Datacollectedregularlyonantimicrobialuseatthelocallevelcanbeusedtocommunicatepatternstoprescriberswhocanthenaccuratelyprescribeantimicrobialstopatients.At national and regional levels, data canbe aggregated to show trendsin resistance and correlations to antimicrobial consumption. At the global level,monitoring can determine the source and contain the spread of emerging resistantmicroorganisms.

In the Western Pacific Region, the burden of diseases that are untreatable withantimicrobialswill continue to increase if nomeasures are taken todiminishAMR,resulting in a risingprevalenceof resistantpathogens.The ability of antimicrobialsto effectively combat infections will be drastically reduced, which would havea detrimental impact on the management of infectious diseases. In addition, theirrationalandfrequentoverconsumptionofantimicrobialsincreasestheriskofdrugtoxicity,antimicrobial-relatedadverseeffectsandincreasedhealth-carecosts.

The combined monitoring of antimicrobial use and the surveillance of resistantmicroorganisms are essential to provide a better understanding of the relationshipbetween consumption and use, and can support important policy changes tocontainAMR.Veryfewcountries in theRegionhavedevelopedsystemstomonitorantimicrobial consumption or use. Unlike surveillance ofAMR, which is done forat least some pathogens inmost countries, very few countries in the Region havecomprehensivereportsonantimicrobialuse.

There are various reasons why the measurement and evaluation of antimicrobialconsumptionremainsachallengeformanycountriesoftheRegion.Theseinclude:• lackofnationalpoliciesthatrequireregularmonitoringofantimicrobialuseand consumption;• lackofanintegratednationalsurveillancesystemforAMR;and• lack of the necessary capacity and resources to systematically collect data on antimicrobial consumption and use at the national level in both the public and privatesectors.

Thelackofinformationonantimicrobialconsumptionhashinderedactionstoreduceantimicrobialuse andAMRprevalence.Evaluationof antimicrobialuse inMember



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States is necessary to establish a baseline and monitor progress towards rationalantimicrobialuse.The informationgeneratedcan thenbeused toencouragepolicy-makerstotakeaction.

2.1 WHO RECOMMENDATIONS FOR MONITORING ANTIMICROBIAL USETherehavebeenseveralWorldHealthAssemblyresolutionsandpublicationsbytheWHOurgingMemberStatestotakeactiononAMR.In1998,AMRwasidentifiedaspart of the resolution on emerging and other noncommunicable diseases (WorldHealthAssemblyresolutionWHA51.17/1998).(16)Theresolutionexplicitlyidentifiedtheneedtomonitorvolumesandpatternsofantimicrobialuse.

In 2001, theWHO Global Strategy for Containment of Antibiotic Resistance identifiedeight areasofwork andmade68 specific recommendations regarding internationalaspects, and emphasized monitoring antibiotic use to contain antibiotic resistance.Recommendationsincluded(17):

•Consider the information derived from the surveillance of antibiotic use and antibioticresistance, includingthecontainmentthereof,asglobalpublicgoodsfor healthtowhichallgovernmentsshouldcontribute.•Encourage governments, nongovernmental organizations, professional societies and internationalagencies tosupport theestablishmentofnetworks,with trained staff and adequate infrastructures, which can undertake epidemiologically valid surveillanceofantibioticresistanceandantibioticusetoprovideinformationforthe optimalcontainmentofresistance.

In2011,AMRwasthethemeofWorldHealthDayandasix-pointpolicypackagewasreleased. (2)Thesecondpointemphasizesstrengtheningmonitoringtotracktheuseandmisuseofantimicrobialmedicinestoassesstheirpublichealthconsequences.

Antimicrobial Resistance: Global Report on Surveillance, published in April 2014,summarizesfindings from129WHOMember States on resistance surveillance anddata forbacteria–antibacterialdrug combinations. (1) The report reveals the lackofstructuresforcoordinationandinformationsharingthatcouldprovideanup-to-dateoverviewof thepresentsituationofAMR.Thereport focusesonthesurveillanceofantimicrobial-resistantorganisms,andnotontheconsumptionoruseofantimicrobials.

InMay2014,theSixty-seventhWorldHealthAssemblypassedresolutionWHA67.25onAMR.Inmonitoringconsumption,MemberStatesareurgedto:•monitor the extent of antimicrobial resistance, including regular monitoring of the use of antibiotics in all relevant sectors, in particular, health and agriculture, includinganimalhusbandry,andtosharesuchinformationsothatnational,regional andglobaltrendscanbedetectedandmonitored;•develop antimicrobial resistance surveillance systems in three separate sectors: (i) inpatients in hospitals; (ii) outpatients in all other health-care settings and the community;and(iii)animalsandnon-humanusageofantimicrobials.

Effectivestrategiesareneededtoimprovetheuseofantimicrobialsinordertocontaindrug-resistantpathogens.Reliableandcomparabledataareneededontheincidence,prevalenceandprescribingpatternsofantimicrobialagents.



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Regular monitoring and quantification of antimicrobial use and consumption areessentialcomponentsofthesurveillancestrategyatthenational,regionalandgloballevelstoaddressAMR.Inparticular,regularmonitoringcanhelptoassessthelinksbetweentheuseofantimicrobialagentsandthedevelopmentofresistantpathogensin humans and animals. The following sections outline the need formonitoring ofantimicrobialuseinMemberStatesoftheWesternPacificRegion.

2.2 PROPOSED REGIONAL SYSTEM TO MONITOR ANTIMICROBIAL USE

2.2.1 GoalThegoal is todevelopand/orstrengthennationalsystemstomonitorantimicrobialuseinordertocontainAMRintheRegion.ThedatacollectedwillprovideevidencetoMemberStatesontheirprogresstowardstherationaluseofantimicrobialsandinformpolicy-makersontheevolvingpublichealththreatposedbyAMR.

2.2.2 ObjectivesThespecificobjectivesareto:•collect data on the consumption and use of antimicrobials at all levels of health care, applying standardized methodologies and using internationally recognized classificationsystemstoensurecomparablemethods;•developindicatorstoregularlymonitorprescribingofantimicrobials,usingup-todate,evidence-basedguidelinestodeterminegoodpracticesforthemanagementof communicablediseases;and•reportdataonantimicrobialconsumptionanduse fromall relevantsectorsat the nationalandregionallevelsonaregularbasis,inordertoinitiatecollectiveactionon containingAMRintheRegion.

2.2.3 Methodology for monitoring antimicrobial use Data collectionThereareavarietyofmethods tocollect,analyseandpresentdataonantimicrobialconsumption and use. A common approach would allow for comparison andmonitoringofprogress in reducingunnecessaryantimicrobialuseat local,national,regionalandgloballevels.

TheAnatomical,TherapeuticandChemical(ATC)classificationsystemandthedefineddailydose(DDD)arerecommendedbyWHOformeasuringdrugutilization,includingantimicrobial consumption. Other methods to measure antimicrobial consumptioninclude measuring by weight, and using financial data or point-prevalence data.Measuring by ATC/DDD facilitates the comparison of consumption informationbetweencountries,regionsandhealth-caresettings,andexaminationoftrendsindruguse over time and in different settings. The DDD corresponds to the average dailymaintenancedoseforadrug’smajorindicationandiscommonlyrepresentedper1000inhabitantsperdaytoaverageusageonapopulationlevel.TheATC/DDDmethodiscommonlyused in theEuropeanUnion(EU),EasternPartnership (EaP)andmembercountries of theOrganisation for Economic Co-operation andDevelopment (OECD).A limitation of thismethod is that it does not provide any indication as towhy theantimicrobialsareusedandwhethertheiruseisappropriate.



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Measuringthetotalquantityusedbyweightcanbeusefulformeasuringantimicrobialuseintheanimalsector.Withvaryingoutletsforthepurchaseofantimicrobialagentsinbulkforanimalhusbandryandlittleregulationtocontrolsales,itmaybedifficulttoobtainthesedata.

Toprovideinsightsintotherationaluseofantimicrobials,point-prevalencedatacanbecollected.EachHCFconductsa“snapshot”surveyonthediagnosisandreasoningforantimicrobialuseforeachpatient.Aparticularbenefitofthepoint-prevalencemethodisitsuniversalapplicabilitytoanytypeofhealth-careinstitution,therebyallowingforbroadcomparisons.

Thequalityuseofantimicrobialscanalsobemonitoredbycollectingdataonsimpleindicators.Forexample,measuringthepercentageofpatientsprescribedantibiotics,especially in areas where systematic monitoring is not in place. Quality use andprescribingpatternscanbemonitoredbyrecordingthepercentageofspecificdiseasecases prescribed antibiotics, for example, patients prescribed antibiotics for upperrespiratorytractinfectionsordiarrhoea.

Other quality use indicators, such as duration of surgical prophylaxis, oral versusparenteraluseandcompliancewithSTG,canbehelpfulformonitoringantimicrobialuse.Localandnationalsurveysapplyingtheseindicatorscanprovidevaluabledataonchangesovertime,andcanshowpatternsofuseandresponsestointerventions.

2.2.4 Data sourcesData on antimicrobial use can be collected from multiple data sources and, withthe application of appropriate analytical methodologies, used at the national andsubregionallevels.Datasourcesinclude:•Sales data.Wholesaledatacanbeobtainedonpharmaceutical salesatanational, subnationalorlocallevel.•Dispensing data (either comprehensive or sampled). Computerized pharmacies can easily collect data on the drugs dispensed.Alternatively, sample data can be collectedmanually.•Reimbursement systems. National-level reimbursement systems that provide comprehensive dispensing data down to the individual prescription can be used. Similardataareoftenavailable throughhealth insurancedatabases.When linked, these databases allow the collection of demographic information on patients and information on dose, duration of treatment and co-prescribing. Less commonly, linkage tohospitalandmedicaldatabasescanprovide informationon indications andoutcomes,suchashospitalization,useofspecificmedicalservicesandadverse drugreactions.Manyhigh-incomecountriesintheRegionhavesophisticated,linked health insuranceordispensingdatabases thatallowdetailedanalysisofantibiotic usepatterns.•Patient encounter-based data. Data are collected by specially designed sampling studies,suchasthosecarriedoutbymarketresearchorganizations(forexample,IMS Healthdata).Theincreasinguseofinformationtechnologyatthemedicalpractice levelwillmakesuchdataavailablemorewidelyinthenearfuture.Thesemethods have the advantage of potentially providing accurate information on prescribed dailydoses,patientdemographics,durationoftherapy,co-prescribing,indications, morbidityandco-morbidity,andsometimestherapyoutcomes.•Patient survey data. Collection of patient data can provide information on drug consumptionand can take into account compliancewithfillingprescriptions and takingmedicationsasprescribed.Patientsurveydatacanalsoprovidequalitative information on perceptions, beliefs and attitudes towards the use of medicines.



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•Health-care facility data. Data onmedication use at all the above levels is often availableinhealth-caresettings,suchashospitalsandhealthcentresatthenational, regional,districtorcommunitylevel.

Need for a common methodologyMonitoringat theregional level isneededtocollectdataandpresentresults fromallMemberStatesonantimicrobialconsumptiontoinformregionaleffortstocontainAMR.Themethodologicalapproachestocollectdataandthesourcesforobtainingdatawilldependonthecountrysetting.Standardized indicatorsareneededtoassessprogressin monitoring antimicrobial use and consumption across the Region. Methods andindicatorsshouldbedefinedthroughexpertconsultationsandamongMemberStates.

When attempting to define ideal levels of consumption, several factors should beconsidered including local disease prevalence, resistance susceptibility patternsand antibiotic prescribing practices.Optimal levels of antimicrobial use to serve astargetlevelswillalsoneedtoberesearchedanddeterminedthroughfutureregionalconsultations.

2.3 GLOBAL SYSTEMS FOR MONITORING ANTIMICROBIAL USEOther WHO regions and international associations have systems in place formonitoring the consumption and use of antimicrobials worldwide. The datacollectedbythesesystemsvary,dependingonthecountryinfrastructureandtypeofhealth-care system, but include data sources from pharmaceutical sales, insurancereimbursements,exportsandhospitals.

2.3.1 Other WHO regionsThere is still a need to gather comprehensive antimicrobial consumption data inmany WHO regions. Most regions have an AMR surveillance network; however,systemsforcollectinginclusivedataonantimicrobialconsumptionwithcomparableindicatorshavenotbeenestablished.Individualstudiesshowtrendsinantimicrobialconsumptionratesinvariousregions,butthisinformationisusuallytakenfromsalesdataofselectcountriesandmaynotbeavailableforallcountries.

The Regional Office for Europe obtainsAMR data from the most well-establishedantimicrobial use monitoring system: the European Surveillance of AntimicrobialConsumption Network (ESAC-Net). ESAC-Net is an EU-funded project managedby the EuropeanCentre forDisease Prevention andControl (ECDC). The networkprovidesdatatotheEuropeanRegionbycollectingnationalstatisticsonantimicrobialconsumptioninhospitalandcommunitysettings.Thedataarecollectedfromnationalsales and reimbursement data, including information from national drug registersin addition to point-prevalence surveys. The network has developed protocols forassessingquantitativeandqualitativepatternsofuse.ESAC-Netdatacanbeaccessedonline via an interactive database and are used in conjunction with the EuropeanAntimicrobial Resistance Surveillance Network (EARS-Net). The data are collectedforthreemajorgroupsofantimicrobials:antibacterialsforsystemicuse(ATCgroupJ01); antimycotics and antifungals for systemic use (ATC groups J02 and D01BA);andantivirals forsystemicuse (ATCgroupJ05).Thedatacollected fromESAC-Netallows countries to audit their antimicrobial use and compare national use with



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other countries reporting to the database. The data show the relationship betweenantimicrobialuseandresistance,andthesummaryreportgeneratedeachyear isanimportanttoolforadvocacyandassessingpolicyguidelines.

TheLatinAmericanNetwork forAntimicrobialResistanceSurveillance (ReLAVRA)is a network within the Pan American Health Organization, which coordinatesbothAMR surveillance andmonitoring of antimicrobial consumption for the LatinAmericanregion.

To better understand usage patterns of antibiotics in developing and transitionalcountries,WHO created a databasewith studies published from 1990 to 2006, andpublished these data inMedicines Use in Primary Care in Developing and Transitional Countries: Fact Book. (18) This database provided insights into inappropriate useof antibiotics, especially for upper respiratory infections and diarrhoeal diseases;however,thesedatawerecollectedfrompublishedstudiesandnoattemptwasmadetoestablishasystemtocontinuouslymonitorantibioticuse.

2.3.2 Other organizationsSurveillance data on antimicrobial consumption are also collected by otherorganizations. The OECD collects the overall volume of antibiotics prescribed inmember countries. These data are obtained only for member countries and arecollectedfromavarietyoforganizations,includingESAC-NetforEuropeancountries,IMSHealthfortheUnitedStates,andself-reporteddatafromministriesofhealthandpharmaceuticalsales.ForMemberStatesoftheWesternPacificRegionwhoareOECDmembers(Australia,JapanandtheRepublicofKorea),aggregatedataontheoverallvolumeofantibioticsprescribed(DDDsper1000)areincludedintheOECDdatabasebut there isnodifferentiationbetween the typesofantibioticsprescribed.Therearealsovariationsinthemethodologyusedtocollectthesedata.Forexample,Australiadoes not report antibiotics dispensed in hospitals, non-reimbursed drugs or overthe counter (OTC)medications,whereas theRepublic ofKorea includes thesedata.DiscrepanciesinmethodologymakeitdifficulttocomparedataacrossMemberStates.ASEAN,whichincludessevenWesternPacificMemberStates,doesnotcollectdataonantibioticconsumptionorprescriptionratesforhumans,ortheuseofantimicrobialsinanimalhusbandry.

2.4 PRESENTATION AND DISSEMINATION OF SURVEILLANCE DATATo improve the use of antimicrobials and contain AMR, antimicrobial use andconsumptionmustbemeasuredtosetabenchmarkandtrackprogresstowardsqualityuseofantimicrobials.Thedatacollectedthroughmonitoringtheconsumptionanduseofantimicrobialscanthenbepresentedinawaythatwillstimulateasenseofurgencyandprovideimpetusforincreasedawarenessandpolicyactions.

2.4.1 Combined surveillance of antimicrobial resistance and useThere is a known correlation between rates of antimicrobial consumption andthe prevalence of AMR. Data monitoring antimicrobial consumption shouldbe used together with AMR surveillance data to track trends in resistance andpredict future susceptibility patterns of resistant pathogens. The data can then beused to improve STGs and influence prescribing behaviour when new resistant



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strains emerge. Monitoring antimicrobial use will also measure compliance withnew treatment recommendations by tracking the volume of first- and second-line antimicrobials that are prescribed. Complementary data on monitoring ofantimicrobial use and surveillance ofAMRwill also allow for long-term temporaland geographical associations that can be easily visualized to support insights andpolicyrecommendations.TheECDCsystem,whichcancombinedatafromEARS-NetandESAC-Net, allows antimicrobial consumptiondata to be linkedwith resistancedata. Analysis requires the system to be harmonized, including entry codes anddenominatordata.

Cost of AMR and irrational use of antimicrobialsThere is evidence that AMR has significant adverse impacts on clinical outcomes,leading tohigherhealth-care costs.The increasedeconomicburdenassociatedwithAMRisattributedtothehigherpriceofantimicrobialdrugsbeyondthefirst lineofdefence and to consuming more health-care resources. Irrational antimicrobial usealsounnecessarilyincreasestheriskofadverseside-effectsofantimicrobials.Studiescarried out in other regions highlight the economic burden ofAMR. However, toassesstheeconomicburden,thecurrentlevelsofantimicrobialconsumptionmustbemeasured.DatageneratedfromanantimicrobialconsumptiondatabasecanalsohelptoquantifytheburdenofAMRonsocietyandhealth-caresystems.

Encouraging effective policiesAntimicrobial monitoring data can be used to improve rational antimicrobial uselocally, inform policies and identify priorities for action at the national level. AsimprovingtheuseofantimicrobialsisakeyelementincontainingAMR,strategiestoreduceantimicrobialusehavebeenprioritized.However,withoutdocumenting thebaselineformonitoringtheeffectsofinterventions,itisimpossibletotrackprogresstowards rational use. Appropriate data on antimicrobial use will inform policy-makerstomakeappropriatedecisions.Forexample,intheRepublicofKorea,itwascommonpractice forantibioticprescribers toalsodispenseantimicrobials.Growingconcernsofhighantimicrobialconsumptionratesandhighratesofresistanceledtoanationalpolicyin2000,whichprohibiteddoctorsfromdispensingdrugs.Subsequently,inappropriateantibioticprescribingwasshowntodecrease. (19)Withoutasystemtomonitortheuseofantimicrobials,therewouldbenoevidencetosupportnewpoliciesandnowaytomeasuretheeffectivenessofthesepoliciesafterimplementation.Lackofsurveillancecanleadtomisdirectedandineffectivepoliciesthatwastealreadylimitedresourcesandprovide inappropriate therapythatcan increasepatientsufferingandincreasehealth-carecosts.

In 2011, China initiated an antibiotic restraining policy and launched a strategy toreduce irrational prescribing of antibiotics. The initiatives limited the variety ofantibioticsgrantedtohospitals,settargetsforthepercentageofantibioticprescriptionsandpenalizeddoctorswhoprescribedantibiotics inappropriately.Regional systemsweredevelopedtomonitorimplementationofthenationalpolicyinhospitalsusingaudits and inspections. Hospitals were publicly recognized for achieving specificantibiotic targets and some hospitals that failedwere publicly criticized. Followingthese initiatives, an IMS Health hospital audit showed that antibiotic use inhospitalsdecreasedby15%aftersixmonthsof initiatingthenewantibioticstrategy.(22) Additionally, data released by the Chinese Ministry of Health indicated thatthe percentage of prescriptions for antimicrobials decreased from 68% to 58% forhospitalized patients and from 25% to 15% for outpatients. (21) The data collectedbytheMinistryofHealthandoutsideresearchorganizationssuchasIMSHealtharepowerful tools to show the effectiveness of China’s antibiotic reforms and enableotherwiseimpossibletracking.Continualmonitoringofantibioticusewillbeneededtotrackthesustainabilityofpolicies.



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Resource mobilization and advocacyData collected via the monitoring network for antimicrobial use are essential toquantify the burden of AMR on society and health systems. Data are needed topromote effective policies and campaigns to improve rational use of antimicrobialsanddedicatetheresourcestosustaintheseinitiatives.Comparisonsbetweencountrieshavealsoprovedtobeanimportantstimulusforqualityimprovements.Measuringantimicrobialconsumptionwillallowindividualcountriestoassesstheirpositioninrelationtoothercountriesandtriggeractionstoimproveantimicrobialprescribing.

2.5 CHALLENGES FOR MONITORING ANTIMICROBIAL USE IN THE REGIONThere are major challenges to monitoring antimicrobial use in theWestern PacificRegion. Some of these are the lack of commitment to support the monitoring ofantimicrobialuse,lackofagreementonthemethodologyforcollectingvalid,reliabledata, and lack of systems infrastructure, including human resources and technicalinputstosupportdatacollection.

2.5.1 Commitment to support monitoring of antimicrobial useThere is a need to commit to developing systems to monitor antimicrobialconsumption. Currently, the majority of surveillance is at the microbiologicallevel – testing resistant microorganisms. As there is a clear relationship betweenthe consumption of antimicrobials and the prevalence of resistant strains,consumption data must be measured. Health-care facilities, pharmacies, industryand interdisciplinary government entities need to collaborate todevelop integratedsystemstoshareinformation.Thecommitmentofallstakeholdersisessential.

2.5.2 Methodology and consistency of available dataAtthemethodologicallevel,eachMemberStatemustensurethevalidityofpopulationexposure to antibiotics. Inadequate or insufficient population coverage may causesignificant bias in data analysis. Under detection bias is also possible in countrieswheredrugcoverageisnotverified,andwheretherearesubstantialOTCsales.

Compliance with the ATC/DDD classification is important. Some countries do notaggregatedataaccordingtotheWHOclassification.Moreover,thereisalackofreportingon new antimicrobials such as telithromycin and linezolid. There are also antibioticsand antibiotic combinations that have no official DDD. If no DDD is assigned, theconsumption of a particular substance is not recorded and leads to underestimationof consumption in that class. Other differences to consider include the variations inantibioticconsumptioninhospitalsandinambulatoryhealth-caresettings.

Apart from agreeing on a commonmethodology tomeasure consumption anduse,thereareotherchallengestocollectingantimicrobialconsumptiondataintheWesternPacific Region. For example, themajority of the data collected are via prescriptionlogs, pharmacy databases, drug purchases or sales, or medicines inventories. Inmany countries of the Region, these data are not available either because they arenot recorded or are owned by manufacturers or pharmacies, which have no legalobligationtosharetheinformation.Consumptiondataisparticularlydifficulttocollectin countries where antimicrobial agents are available OTC without a prescription.Obtainingthisinformationalsodoesnotnecessarilyreflectthetotalamountconsumed



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if the patient does not have access to the medication, does not complete the fulltreatmentcourse,orsharesthecoursewithanotherpatient.

2.5.3 Lack of systems infrastructureDeveloping a monitoring system and network will require appropriate humanresources and technical support. Many Member States in the Region do not havesystemsfortrackingantimicrobialusedata.Systemswillthusneedtobedevelopedand implemented in conjunction with efforts to strengthen health systems. Whenpossible, new monitoring systems should be linked to existing systems, andmechanismstoincorporatedataintoeachcountry’shealthinformationsystemshouldbe explored. Finally,when developing a network formonitoring antimicrobial use,MemberStatesmustalsoagreeonissuesofdataownership,confidentialityanduse.MemberStateshave the responsibility tomonitor antimicrobial consumptionat thenational level andsharedataat a regional level fora collective response to containAMR.

2.5.4 Linkage of antimicrobial use in animal husbandryWHOhasaroleinestablishingformalmechanismsfordatasharingbetweenhealthauthorities,theveterinarysectorandfoodauthoritiestoreduceantimicrobialuseandcontainthespreadofresistantbacterialstrainsthroughfood,animalsandagriculture.TheOIEandFAOare importantstakeholders for furthercollaborationonantibioticconsumptionandmonitoring.

There is a need to extend the collaboration and agreement between FAO,OIE andWHOatthegloballeveltotheregionallevel,inparticular,regardingdatacollectionfor antimicrobial use in the animal husbandry sector. The Regional Office for theWesternPacificwillcollaboratewithFAOandOIEonhowconsumptiondatafromtheagriculturalsectormaybecollectedanddisseminated.

2.6 THE WAY FORWARDThereisaneedtodevelopanintegratedsystemtoregularlymonitortheconsumptionanduseofantimicrobialsintheWesternPacificRegion.Informationonantimicrobialuseandconsumptionshouldbesharedacrosssectorstoinformnationalandregionalpolices and strategies to reduce unnecessary antimicrobial use. The next steps formonitoringantimicrobialuseare:

(1) toconductacountrysituationandcapacityanalysistodeterminetheavailabilityofreliabledataonantimicrobialconsumptionanduseintheRegion;

(2) forcountrieswithlittledata,todevelopastrategytoprovideadviceonpoliciesandcapacity-buildingtosetupsystemstocollectdataformonitoringantimicrobialconsumption;

(3) to develop a common methodology for Member States in the Western PacificRegionandtrainlocalstakeholdersinitsuse;and

(4) to encourage resource mobilization to build a regional database and developcountrycapacitytomonitorantimicrobialconsumptionanduse.


Health systems response to support containment of antimicrobial resistance


HEALTH SYSTEMS RESPONSE TO SUPPORT CONTAINMENT OF ANTIMICROBIAL RESISTANCE

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3. Health systems response to support containment of antimicrobial resistanceItisessentialtostrengthenhealthsystemsinordertocontainAMR.Nationalplansto containAMR need to consider strategies that strengthen health systems overall,suchasIPCprogrammesinhospitalsandhealthfacilities,educationandtrainingofhealth-careprovidersusingpre-serviceandin-servicecurriculathataddressAMRandrational antimicrobial use, and establishment of effective antimicrobial stewardshipprogrammes. Health system responses also need to cover public awareness andeducationcampaigns,theformulationandenforcementofAMR-relatedpoliciesandregulations,strengtheningtheregulatoryframeworktoreduceabuseofantimicrobials,and institution of surveillance of antimicrobial use and resistance, in addition tostrengtheninglaboratorycapacity.Inmostcountries,thereisalackofacomprehensive,multisectoral policy and regulatory framework to contain AMR, in particular,antibioticresistance.Betterregulatorysystemswitheffectiveenforcementmechanismsareneededtoimprovetheappropriateuseofantimicrobialagentsinallsectors.

Pharmaceutical systemThe emergence of AMR is a complex problem driven by many interconnectedfactors, in particular, the use and misuse of antimicrobials. In turn, antimicrobialuse is influenced by the interplay of knowledge, expectations and interactions ofprescribers and patients, financial incentives, the characteristics of health systemsand the regulatory environment. Given this complexity, coordinated interventionsare needed to simultaneously target the behaviours of individual stakeholdersand theenvironments inwhich they interact (Fig. 2). Strategies toaddressdifferentcomponents of health systems and drug supply chains can reduce antibioticconsumption,therebylimitingthedevelopmentandspreadofAMR.

Figure 2. Health systems perspective and structures influencing the use of antibiotics

Source: Compiled from: Nordberg P, Stålsby Lundborg C, Tomson G. Consumers and providers – could they make better use of antibiotics? Int J Risk Saf Med. 2005;17:117–25.

National governments

Political engagement and leadershipMonitoring and enforcement

Economic incentivesHealth systems infrastructure

Pharmaceutical policy

Health-care

facilities Regulatoryagencies Dispensers

Patients



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Responsible use of antimicrobials Consumption of antimicrobials correlates with the prevalence of AMR. Bothoveruse and underuse of antibiotics can lead to resistance. Therefore, promotingthe appropriate and responsible use of antimicrobials is one of the most urgentinterventionsneededtoreduceAMR.

Rationaluseofmedicinesminimizesthemorbidityandmortalityduetoantimicrobial-resistant infections by preserving the effectiveness of antimicrobial agents as atherapeuticoption.ThechoiceofantimicrobialsshouldbeguidedbylocalornationalresistancesurveillancedataandSTGs. IntheWesternPacificRegion,69%ofMemberStates responding to the country situation analysis (CSA) have at least one disease-specificAMR surveillance programme; however, only 22%have a coordinatedAMRsurveillanceprogrammeatthenationallevel.Sixty-twopercentofMemberStateshaveadefinedprocess for thedevelopmentofSTGs forantimicrobialuse.Rationaluseofantimicrobials shouldbepromoted through strategies that strengthenhealth systems,andbyimplementingandenforcingnationalregulationsinvolvingantimicrobialuse.

ThereisalackofcurrentdataonantimicrobialconsumptionfromallMemberStatesin theWesternPacificRegion.However, studies fromChinaandVietNamindicatethatantimicrobial consumption ishigh. (22,23)Compared tootherOECDcountries,Australia and the Republic of Korea have higher antibiotic consumption than theOECDaverage,i.e.24.1and27.0DDD/1000population/day,respectively,versus20.9DDD/1000population/day.(24)

Less than half the Member States in theWestern Pacific Region (48%) report thatantibiotic use has been monitored in the past five years. Financial or prescriptiondatacanprovideevidencetoshowconsumptionlevelsofantimicrobials,butitisasimportant to knowwhether or not the antimicrobial agent has been appropriatelyprescribed and consumed. In conjunction with monitoring trends regarding theprevalence of drug-resistant infections and pathogens, monitoring of antimicrobialconsumptionisalsonecessarytounderstandthetrendsinAMR.

3.1 REGION-SPECIFIC CHALLENGES IntheWesternPacificRegion,healthsystemcharacteristics,expectationsandinteractionsof prescribers and patients, economic incentives and the regulatory environment allcontributetoAMR.Thereiswidevariationbetweencountrieswithrespecttohealth-carefinancingmechanisms, availability of health facilities, services and a competent healthworkforce,andaccesstoqualityessentialmedicinesandhealthtechnologies.AlloftheseimpacthowpatientsandprofessionalsuseantimicrobialswithconsequencesforAMR.

2.1 Lack of strategies at the health systems level Containing AMR requires strengthening of health systems. Developing nationalantibiotic policies, STGs and establishing essential drugs lists or formularies canencouragetherationaluseofantimicrobialsandpromoteproperaccesstothem.Keyinformant interviews in the Western Pacific Region acknowledge that althoughSTGs exist in many countries, there is little connection between adherence tothese guidelines and accreditation or licensing. (25) Health-care workers oftenlack sufficient training and supervision to prescribe rationally and contribute toimproperantimicrobial-prescribingpractices.AreportfromSingaporeofvancomycinand carbapenem audits showed that 23.5% and 44% of these, respectively, wereinappropriatelyprescribed.(26)



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Only31%ofMemberStatesreportthathealth-careworkershaveahighawarenessofAMR.Prescribersmustadoptandabidebyclinicalpracticeguidelinesandmonitorprescribinghabits.Only10MemberStatesintheRegionreporthavingamechanismtodoso.InChina,thepercentageofprescriptionscontainingantibioticsinruralclinicswasaround50%–thisishigherthaninothermiddle-andhigh-incomecountries. (27)

Weakinfrastructure,includingpooraccesstorapiddiagnostictests,makesitdifficultforlaboratoryresultstosupporttreatmentdecisions,furthercontributingtoimproperantimicrobialuse.Withhighdiagnosticcostsandpooravailabilityofgooddiagnosticservices,itissometimeslessexpensivetoprescribeanantibioticfortreatmentthantoorderlaboratoryresultstovalidatethecorrecttreatment.AstudyinawesternprovinceofChina found that bacteriology sampleswere rarely takenbefore antibioticswereprescribed.(28)Whileempiricaltreatmentisoftennecessarybecauselow-costpoint-of-care diagnostics suited for resource-limited settings are currently not available,strengthening laboratory diagnostic capacity is an important requirement formoreaccurateandappropriateuseofantimicrobials.

Strengthening health systems will require political commitment and financialinvestments, but the health and economic burden associated with AMR can behigher,especiallyinlow-incomecountries,andthereforesuchinvestmentsmaybringsubstantial returns. Surveillance andmonitoring of antimicrobial use is integral toprovideinformationonmicrobiologicalsusceptibility.

3.1.2 Expectations and interactions of prescribers and patientsPatientbehaviour, includingmisperceptions, expectations, self-medicationandpooradherencetodosageregimens,contributestoAMR.Often,patientsareunawareofthepharmacologicalactionsofantimicrobialagentsandthereforedonotunderstandwhenorhowtheyshouldbeused(Box1).

Box 1. An innovative approach to antimicrobial stewardship in Australia (29)

The National Prescribing Service of Australia (NPS MedicineWise) designsbehaviour change interventions to improve the use of medicines and healthtechnologies.Thegoalistoprovidehealthprofessionals,consumers,governmentofficials and industry with evidence-based information to support informeddecision-makingonmedicineuse.

In February 2012,NPSMedicineWise launched a five-year campaign againstantibioticresistancewithastrongemphasisoncommunityeducationandwiththegoalofreducinginappropriateprescribingofantibioticsinAustraliaby25%in five years.Using an innovative,multimedia approach, including outreachactivities through social media, television spotlights, local celebrities andtraditionaladvertising,thecampaignaimstoeducatethepubliconAMRandempowerthemtobepartofthesolution.

ApreliminaryevaluationofthecampaignshowsanincreaseinAMRawarenessinAustralia;however,moretimeisneededtoevaluatethelong-termimpactsofthecampaignsonchangingconsumerbehaviourstowardsantimicrobialconsumption.Patientbehaviour,includingmisperceptions,expectations,self-medicationandpoor adherence to dosage regimens, contributes toAMR.Often, patients areunawareofthepharmacologicalactionsofantimicrobialagentsandthereforedonotunderstandwhenorhowtheyshouldbeused.



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Interactions between prescribers and patients also influence antimicrobialusage.Oftenpatientsspendlittleornotimewithahealth-careproviderbeforereceiving antimicrobial therapy. Providers feel pressure to treat patientswithantimicrobialsandthereforeunnecessarilyprescribeantibioticstosatisfythem.Providershaveaninterestinquicktreatmentoptionsasithelpstoattractandretainpatients.Providersmaythuschoosetheshortestcourseoftreatmentoroptforthenewer,moreexpensiveantimicrobials.(30)

Figure 3. Patient awareness of mode of action of antibiotics in Malaysia

Patients who purchase antimicrobials without a prescription may not receive thenecessary therapeutic instructions from a licensed prescriber. A study in Malaysiashowedthat67%ofpatientsincorrectlybelievedthatantibioticsareeffectiveagainstviralinfections(Fig.3).Bettercommunicationandpatienteducationcanimprovetherationaluseofantibioticsanddiscouragepatientsfromabusingantimicrobials.

3.1.3 Financial incentives that encourage overuse and overprescribingFinancial incentives canencourageoverprescribingof antimicrobials, leading to thedevelopmentofAMR.InChinaforexample,wherepharmaceuticalsalesareadirectsourceofincomeforhospitalsandhealth-careproviders,theremaybeanincentivetooverprescribe.(30)Evidenceshowsthatwhensuchperversefinancial incentivesareremoved,alongwithimplementationofotherinterventionsaspartofthenationwidespecial antibiotic stewardship programme in China, significant reductions can beachievedintheoveruseofantibiotics. (32)

Pharmaceuticalcompaniescaninfluenceprescribinghabitsbyofferingprofit-sharingtoprescribers. Physicianswhodispensemedicationsmay alsohave an incentive tooverprescribe.IntheRepublicofKorea,anationalpolicythatprohibiteddoctorsfromdispensing drugs in 2000was shown to selectively reduce inappropriate antibioticprescribing. (33) This example provides evidence that prohibiting medicationdispensingbyphysicianscancontributesignificantlytopromotingthequalityofdruguse. Local incentive structures should be examined to identify incentives thatmayinfluenceantimicrobialprescribingpractices.

Financialincentivesthatencouragetheoveruseofantibioticsalsoexistinveterinarymedicalpracticeandinanimalhusbandry.STGsshouldbeusedtoestablishmethodsofpaymentandreimbursement,andfinancialincentivesthatpromoteoverprescribingshouldbeeliminated.

Believe antibiotics are effectiveagainst viral infections

Expect antibiotics prescribedfor common cold syptoms

No33%

Yes67%

No53%

Yes47%

Source: Compiled from: Nordberg P, Stålsby Lundborg C, Tomson G. Consumers and providers – could they make better use of antibiotics? Int J Risk Saf Med. 2005;17:117–25.



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3.1.4 Poor awareness and civil society engagementEducation and awareness among those involved in antimicrobial use is vital.These include policy-makers, regulators, the pharmaceutical industry, prescribers,dispensersandconsumers.IntheWesternPacificRegion,awarenessofAMRislacking.Publicawarenessisreportedtobeabsentorverylowamong93%ofMemberStates.Atthenationallevel,informationcanbeincorporatedintoawarenesscampaignsandantibiotic stewardship programmes to promote prudent use of antibiotics. ElevenMemberStatesintheWesternPacificRegionreportthatapublicawarenesscampaignforantimicrobialusehasbeenimplementedwithinthepasttwoyears.

InastudyofchildreninanurbancommunityinMongolia,42%ofthechildrenweregivennon-prescribedantibioticsbytheircaretakers.(34)ThispercentageishigherthansimilarreportsfromVietNam(35) and China. (36)Thestudyhighlightedthatmotherswithabetterknowledgeofantibioticswerelesslikelytogivetheirchildrenantibioticswithoutaprescription,emphasizingtheneedforpubliceducationonantibiotics.

Information that is unbiased and independent from promotional activities orpharmaceutical companies should be provided to consumers and prescriberson antimicrobial use. Together with regulations on antimicrobial use, awarenesscampaigns and continuing education can enhance the knowledge and attitudes ofconsumersandprescribers,andimproveantimicrobialuse.TocontainAMR,policy-makersandregulatorsmustalsobeeducated to implement thenecessary legalandregulatoryframeworksforpharmaceuticalpromotionanditspotentialadverseimpact.

3.2 IMPROVING REGULATIONSHealth and pharmaceutical regulations shape the way in which antimicrobials areused. In theWestern PacificRegion,many countries do not have a solid legal andregulatoryframeworktomandate,supportandenforcetherationaluseofmedicines.Countries with weak regulatory systems have limited capacity for ensuring drugquality,improvingdispensingofmedicines,restrictingtheuseofantibioticsinanimals,andcontrollingthemovementofdrugsinthesupplysystem.

3.2.1 Ensuring qualityControllingthequalityofallantimicrobialsisessentialforsafeandeffectivedeliveryto patients. Through regulations,Member States can control the quality, safety andefficacy ofdrugs.Counterfeit, substandard ordegraded antimicrobials are likely todrivedrugresistance.Antimicrobialscontaininglessthanthestateddosemayresultin therapeutic failures and selection of drug-resistant strains. Counterfeit productscommonly contain little or none of the active substance stated on the label ormaycontain an entirely different active ingredient. A counterfeit drug with no activeingredientwillnotdirectlyfacilitateselectionofantibiotic-resistantbacteria;however,resistantbacteriamaystillemergeiftheactiveingredientsincludeotherantibiotics.Through regular inspections, governments can ensure that drug manufacturersadheretogoodmanufacturingpractices(GMP),productspecificationsandlicensingrequirements.Countrieswithoutsystemsforcontrollingthequalityandassessingthesafetyandefficacyofdrugsfaceanincreasedriskofexposuretosubstandard,inferiorandcounterfeitdrugsthatpenetratethemarket.

Substandard medicines that may contain lower amounts of active ingredientsor fail to deliver (due to poor dissolution, dispersion of tablets, injections) the



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required amount of active ingredient are a particular threat for increasing theemergence of resistant bacteria. In countrieswhere regulatory capacity is limitedto ensure adherence toGMP,manymanufacturerswithdeficient and inconsistentmanufacturing practices may sell poor-quality, substandard products legally innational,regionalandinternationalmarkets.

In theWesternPacificRegion,68%ofMemberStatesreporthavingnationalqualitystandardsforantimicrobials;however,only40%ofMemberStatesreportthattherearespecialmechanismsfordetectingandcombatingcounterfeitmedicines.EnsuringthequalityofavailableantimicrobialscanreducetheriskofAMR.

3.2.2 Improving dispensingInmanycountriesoftheWesternPacificRegion,antimicrobialsarecommonlydispensedbyunauthorizedpeoplewho lack theappropriate training.Overhalfof theMemberStates in the Region report that antimicrobials are sold OTCwithout a prescription.Key informant interviews in theRegion revealed thatmany countries have laws fortheaccessibilityofantimicrobialsonlybyprescription,buttheselawsarenotenforcedadequately. (25) For example, inMongolia, aministerial decree announcedmeasurestostopOTCsalesofnon-prescribeddrugsin2011,butinpracticeitcontinues. (37) As poorenforcementofprescription-onlyregulationsisalmostuniversallyassociatedwithinappropriate antimicrobial usage, regulation to limit non-prescription dispensing ofantimicrobialsiscrucialtocontrollingtheemergenceofAMR(Box2).

Box 2: Developing a road map for antimicrobial stewardship in Viet Nam

In 1986, Viet Nam implemented several market-based reforms, includingprivatizationofthepharmaceuticalindustryandderegulationoftheretaildrugtrade.Followingthereforms,thenumberofprivatepharmaciesincreasedfromzeroto6000between1986and1992.Duringthesameperiod,therewasasix-fold increase in the annual per capita consumption of pharmaceuticals,withantibioticsrepresentingthehighestproportionoftheincrease.(38)

Good Pharmacy Practice (GPP) standards were issued in 1997 to improvestandards. These required pharmacies to monitor drug quality, recordconsumptionandcomplywithprescription-onlyregulations.GPPpharmaciescontinued to dispense antibiotics to patientswithout a prescription.A studyofantimicrobialusewasconductedinHanoifrom1997to2000,followingtheimplementationofaseriesofinterventionsin68privatepharmacies.(39) Thestudy indicated that improvements inprivatepharmacypractice arepossiblewith a combination of enhanced regulatory enforcement, education andpersonalinvolvementthroughpeernetworks.

In 2012, the Viet Nam Resistance (VINARES) project was launched to buildthe capacity of health workers and strengthen AMR stewardship in health-care settings. The VINARES programme aimed to control hospital-acquiredinfections,preventirrationalantibioticconsumptionandstrengthenlaboratorysurveillance. The stewardship programme is currently being implementedthroughtrainingworkshopswithsupportfromVINARES.However,inthelongterm,throughcapacity-building,theprogrammeaimstoequiphospitalswiththetoolstoconductself-sufficientantimicrobialstewardshipprogrammes.(40) TheVINARESprojectcouldserveasamodelframeworkforothersettings.



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While regulations should be enforced to limit OTC sales, patient access to high-qualityantimicrobialsmustbeensuredthroughprescriptionofappropriatetreatmentregimens by trained health-care workers. Often, patients seek treatment frompharmacists and drug sellers who are not trained to diagnose or prescribe. Goingdirectlytothepharmacistoftencostslessandislesstimeconsumingthanfirstseeingalicensedhealth-careworker.EnforcingregulationsthatprohibitOTCsalesiscriticalforpromotingtherationaluseofantibiotics.

The way antimicrobials are packaged and dispensedmay also contribute toAMR.Antimicrobial tablets that are sold individually, rather than in the full treatmentcourse,maypromote theunderuseofantimicrobials, leadingto thedevelopmentofresistant strains.Limitedfinancialmeans is alsoa factor, aspatientsoftenpurchaseonlyasmuchmedicationastheycanafford,andmaystopthetreatmentcourseoncetheybegintofeelbetter.Studieshaveshownthatanestimated90%ofconsumersbuythreedays’supply,orless,ofantibiotics,makingcompliancewiththerecommendeddosage impossible. (41)Packaging regulations that require full treatment courses tobedispensed, inadditiontoeasy-to-readpackagelabelswithsymbols,canimprovepatientadherenceandlimitAMR.

3.2.3 Regulations to restrict the use of antibiotics in animalsAntimicrobialuseinfood-producinganimalsaffectshumanhealthduetothepresenceofactiveantimicrobialresiduesinfoods,andparticularlybytheselectionofresistantbacteria in animals. The consequences of such selection include an increased riskof development of resistant pathogens, the vertical spread ofmicrobes harbouringresistancegenesbetweenanimals,aswellastheirtransfertohumans

The underlying principles of appropriate antimicrobial use and containment ofresistance are similar to those applicable to humans. A “OneHealth” approach isrequiredtocoordinatethefood,veterinaryandhealthsectorsatthenationallevel.Thenational regulatoryauthority in66%ofMemberStates in theRegiondoesnothavemechanisms in place to enforce requirements for rational use of antimicrobials inanimals.Likewise,thereisalegalprovisiontoreducetheuseofantibioticsasgrowthpromoters for food animals in only 32%ofMember States. Enhanced collaborationbetween veterinary and human medicine would accelerate interdisciplinary andinternationalactiontocontainAMRthroughaOneHealthapproach.

3.2.4 Securing the supply of effective, quality antimicrobials through regulationThe ability of prescribers and dispensers to provide appropriate, high-qualityantimicrobial agents is determined by the consistent supply of the necessaryantimicrobials.Theroleofgovernmentregulatorsistoensureaccesstogood-qualitymedicinesandsecurethesupplychainfromthemanufacturertothepatient.Often,thedrugsupplychainisinadequatelysecuredduetolimitedorinappropriateregulationrelatedtotheprocurement,storageandsalesofqualityantimicrobials.Additionally,intheWesternPacificRegion,withonly32%ofMemberStatesreportedtomanufactureantimicrobialmedicinesintheircountry,itisnecessarytostrictlyenforceimportationrequirements and inspect the quality of medications. The individual steps in thesupplychaincancontributetoAMRifnotproperlyregulatedandenforcedacrossboththepublicandprivatesectors.



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3.3 STRENGTHENING INFECTION PREVENTION AND CONTROLIPCprogrammesareimportantinpreventingthespreadofinfectiousAMRpathogenswithin and between HCFs. Resistant microorganisms also easily spread fromHCFs to the community and to other countries through international andmedicaltourism.IPChasanintegralroleincontainingAMR,asitcanpreventtheacquisitionand transmission of, and infection by, resistant strains of microorganisms, andinadvertentlyreduceantimicrobialuse.The2001WHO Global Strategy for Containment of Antimicrobial Resistance recommended that all hospitals establish IPCs withresponsibility for effective management ofAMR. (17) IPC was further highlightedby the 2011World Health Day policy package, which identified enhanced IPC asimportant for thecontainmentofAMR. (42) In2012, theneedfor IPC inHCFswasfurtheremphasized in theWHOpublicationentitledEvolving Threat of Antimicrobial Resistance: Options for Action. (43)

Successful IPC programmes in HCFs and the community require infrastructure,human resources, financial commitment, protocols and practices, monitoring andevaluation, and linkageswith public health services. Screening patientswithAMRandusing isolationmethodsfor infectedpatientscanfurtherassist tocontainAMR.IPC programmes go hand in hand with laboratory testing to inform the need forpatient isolation and antimicrobial susceptibility testing, surveillance of AMR andantimicrobialuse,aswellasgoodantibioticstewardship.

The spread of resistant pathogens in hospitals and other facilities contributessignificantlytotheincreasingglobalburdenofAMR.InterventionstobringaboutsystemchangeinHCFsinvolveimprovinginfrastructure,ensuringadequatehumanresources,andcollectingappropriatedataformonitoringandevaluationtoinformIPCpractices.

3.3.1 Region-specific examplesMany facilities in the Western Pacific Region have made good progress inimplementing recommendations on IPC, but there are still marked differences inthelevelofimplementationwithinandbetweencountries,inparticular,inlow-andmiddle-incomecountries.This contributes significantly to the inequalities inhealth-care delivery, and spread and containment ofAMR pathogens. (44) StrengtheningcurrentIPCprogrammesanddevelopingnewonesinareaswherethesearelackingareimportanttocontainAMRattheglobal,regional,nationalandlocallevels.

In theWesternPacificRegion, 85%ofMember States report that there are nationalguidelines for IPC inHCFs,with 60%ofMemberStates reporting that theyhaveanational IPCprogramme.With regard toAMRcontainment, 74%ofMemberStateshavespecificIPCmeasuresinplacetocontrolAMRinhospitals.AlthoughtherehavebeenimprovementsinthedevelopmentofIPCprogrammesinthehealth-caresetting,IPCpolicies are lacking in the animalhusbandry sector,with only 32%ofMemberStatesintheRegionreportingthattheyhavetheseinplace.

Inadequate infrastructure and human resourcesApplyingthecoreelementsofIPCinHCFsistheessentialfirststepinIPCstrategiesand in limiting the spread of resistant microorganisms. Deficiencies in HCFinfrastructure, alongwith insufficiently trainedhealth-careworkers tomanage IPC,aremajorbarrierstoimplementingIPCprogrammes.



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Figure 4. Results of a country situation analysis on IPC guidelines and programmes to address AMR in the Western Pacific Region

Source: World Health Organization. Rapid assessment tool for country situation analysis on antimicrobial resistance in Western Pacific Region. Unpublished data. 2013.

HCFinfrastructure,equipment, suppliesandresourcesareneeded toenableeffectiveIPCpractices,includingAMR-containmentmeasures.Seventy-fourpercentofWesternPacificMemberStatesreportedhavingincorporatedthecontrolofAMRintotheirIPCpoliciesinhospitals(Fig.4).EffectiveandfeasibleimplementationstrategiesareneededtotranslatetheseIPCpoliciesandrecommendationsintobestpractices.Implementationrequires situation analyses at the national and HCF levels to set realistic goals andstrategiesforprogressiveimprovementsinIPCwithinthelocalcontext.ThereisalsoaneedforaclearstructureorcommitteeinthehospitalsettingunderwhoseauthoritytheIPCprogrammesexist.DesignatedAMRfocalpointsshouldbeapartofthecommittee.Antimicrobial stewardship committeeshave successfully set upAMR subcommittees,andasimilarapproachisrequiredforIPCcommittees.

Inadequate awareness among health-care workers of AMR transmission dynamicsand prevention methods are additional challenges in implementing IPC practices.With only 31% ofMember States reporting high awareness ofAMR among health-careworkersintheWesternPacificRegion,ongoingeducationandfeedbacktostaffisnecessarytomaintainstandardsandcompliancewithIPCpractices.AMRmustalsobe incorporated into thebasicmedical, nursing andpharmacy curricula to educatefuturemedicalpractitionersandensurethattheyareawareoftheimportanceofIPCtocontainAMR.

Inadequate data on AMR infectionsThelackofsurveillancedataonresistantmicroorganismsintheWesternPacificRegionlimits the implementationof effective IPCpractices to containAMR.Themajorityofthe available data is restricted to high-income countries. Infectious disease incidenceandprevalenceratesatthenationalandindividualHCFlevelsareessentialtoidentifyandprioritize IPCpractices to containAMR;however,microbiology capacity qualitycontrolsareoften limited.PoorlyestablishedAMRsurveillancesystemsmay lack thedatatoassessthemagnitudeofharmtopatients,ortheadditionalresourcesrequiredtomanagehospital-acquiredinfections(HAIs),especiallyresistantpathogens.Datafromcommunity-acquiredinfectionsduetoresistantmicroorganismsisevenmorerare.

National Guidelinesfor IPC in HCFs

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ThelackofstandardizedmethodsanduniversallyapplicablestandardsformeasuringHAIs makes it difficult to assess the current situation, especially when comparingbetween and within HCFs, or attempting to measure the effectiveness of differentinterventions. Accepted methods largely require laboratory support and qualityassurance programmes to effectively collect clinical data. In addition to surveillance,rapiddiagnostic testing isessential to identifyasymptomaticcarriersand/orpatientsinfectedwithdrug-resistantpathogenstoallowtimelyimplementationofIPCmeasures.

Lack of information on costs and cost-effectiveness of infection prevention and controlInformation that addresses the cost–effectiveness of infection control interventionsin containingAMR is limited. The health and economic consequences ofAMR arehigh, though they are difficult to quantify, as the data available are incomplete inmanycountries.Mostof thedataon theeconomicburdenofantimicrobial-resistantinfections in hospital settings have been limited to high-income countries. In theWestern Pacific Region, comprehensive studies assessing the cost–effectiveness ofinterventionshavenotbeenpublished. Thecostsforspecificinterventionsmayvaryconsiderably,dependingonmultiplelocalfactors.Toquantifythesavingsresultingfromtheinterventions,avarietyoflocalissuesneedtobetakenintoaccount,includingthepre-interventionburden,theeffectivenessofinterventionsandpotentialdirectsavingsforhealth-caresystems,aswellassavingsforsocialsecuritysystemsand/orincreasedproductivity.Thepotentialdirectsavingsfor health-care systems include shorter hospital stays, fewer readmissions, reduceddiagnostic tests andneed for antimicrobial treatment.Research is needed todeveloptoolstoevaluatetheimpactandcost–effectivenessofIPCmeasuresincontainingAMRinindividualMemberStatesoftheWesternPacificRegion.

3.3.2 Implementing core elements of IPC in health-care facilities Hospital patients are a main reservoir of resistant microorganisms and it is thusimportanttoimplementcoreIPCelementsinHCFs.

TherearemultipleelementstotheimplementationofsuccessfulIPCprogrammestoreduceHAIsandpreventtheemergenceofAMR,and/ordisseminationofresistantstrainsofmicroorganisms.ThedevelopmentofIPCguidelinestocontainAMRissite,areaandpathogenspecific. IPCprogrammesshouldbe locally tailoredwithgoalsannouncedtohealth-careworkersthroughawarenesscampaigns,andIPCelementsprioritizedaccordingtofeasibilityatthelocallevel.Theseshouldalsodemonstratethe cost–effectiveness of IPC interventions, for example, in reducing the costassociatedwiththeburdenofdiseaseandthelengthofhospitalstay.

A formal organizational structure to facilitate the development and maintenance ofIPCpolicies and strategies is essential.Amultidisciplinary IPC committee shouldbeestablished to develop and support IPCprogrammes. Following the implementationof IPC practices, a monitoring and evaluation framework should be in place toenabletimelyadaptationofIPCstrategiestocurrentneeds.Thereisalsoaneedforanappropriate infrastructure toapply IPCpractices, including theavailabilityofqualityproductsandequipment(gloves,masks,gowns,etc.).Qualitymicrobiologylaboratoryservicesarealsoneededtoinformtheprescriptionofcost-effectiveantimicrobialsaswellasrapidandaccuratedetectionofresistantmicroorganismsfortimelyimplementationofIPC.CollaborationbetweenIPCprogrammesandmicrobiologylaboratories,includinginformation on AMR surveillance, will enable rapid detection and containment ofcurrent and emerging drug-resistant microorganisms. Active linkages between IPC



44

programmes/committeesandpublichealthservicesorothersocietalbodiescanfacilitatecommunicationaboutAMRatthelocal,nationalandregionallevels.CollaborationcanencouragemultifacetedsolutionstocontainAMRandimprovepatientsafetythroughstandardIPCpractices,bothinhospitalandcommunitysettings.(44)BasicIPCpracticesshouldalsobepromotedamongthegeneralpopulation.(25)

Standard precautions for infection prevention and controlStandard precautions include basic hand hygiene, sterilization and disinfection ofmedicalmaterials, prevention andmanagement of injuries from sharp instruments,and a safe and effective waste management system. The promotion of good handhygiene practices will limit the transmission of microorganisms, including AMRisolates, carried on the hands of hospital staff, visitors and patients. Examples ofresistant bacteria primarily transmitted between staff and patients are methicillinresistantStaphylococcusaureus(MRSA)andvancomycin-resistantenterococci(VRE).

Morecomplexinterventionsareneededforsomemicroorganisms,suchasMDRGram-negativebacteria. (44)Currently,eightMemberStates in theWesternPacificRegionhavesignedtheWHOFirstGlobalPatientSafetyChallenge(GPSC)pledgedocumenttocommittoreducingHAIs.TheGPSCprogrammealsoissuedtheWHOGuidelinesonHandHygieneinHealthCareaspartoftheWHOglobalannualcampaignSAVE LIVES:CleanYourHands(Box3).(45)

Box 3. WHO SAVE LIVES: Clean your hands – the Malaysia Story(45)

AspartofaglobaleffortbyWHOtosupporthealth-careworkersinimprovinghand-hygienepractices and reduceHAIs, SAVELIVES:CleanYourHands ispartoftheWHOFirstGlobalPatientSafetyChallenge“CleanCareisSaferCare”launchedin2005.Currently,132MemberStateshavesignedthepledge,eightofwhichareMemberStatesintheWesternPacificRegion.

TheMinistryofHealthofMalaysiajoinedtheCleanCareisSaferCarechallengeand has experienced a gradual increase in the hand hygiene compliancerateovertime,from56.6%inJune2008to82.2%inthefourthquarterof2012.ThiswasaccompaniedbyareductioninHAIsfrom3.57%per100patientsinMarch2007to1.15per100patientsinSeptember2012.Anobligatoryhygieneawarenessdayisheldinmosttertiaryhospitalseveryyeararound5May.



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Together with hand hygiene, barrier practices are also a large component of IPC.Barrierpractices, includingpatient isolationandtheuseofgloves,gownsormasks,arewidelyrecommendedforthecontrolofendemicAMR.Barrierpracticescannotbythemselvesfullypreventorcontaintheprogressionofresistance.(46)Inaddition,goodpractices need to be observed for theprevention andmanagement of injuries fromsharpinstrumentsaswellassafeandeffectivewastemanagement.

Screening of patients for AMR bacteriaAnotherimportantelementofIPCpracticesforthecontainmentofAMRistheaccurateand timely identification of patients infected with drug-resistant pathogens, inparticular,AMRbacterialinfections.Asculturecantakeuptothreedaystoprovideadiagnosis,thereisaneedforrapiddetection.Forexample,theuseofrapidmoleculartesting methods to test for MRSA and MDR-TB is required for timely diagnosis,ensuringcorrecttreatmentandisolationmeasuresifneeded.

Isolation of patients infected with AMR bacteriaTherapidspreadofresistantmicroorganismsisfacilitatedbythetransferofpatientsbetweenwardsandbetweendifferentHCFs. (44)Dependingonthemicroorganism,isolationofpatients,suchasthosewithMDR-orextensivelydrug-resistant(XDR)-TBmayberequired.Thespatialseparation/isolationofpatientsgoeshandinhandwithphysical barriers to reduce the chance of transmitting infectious diseases betweenpatientsand/orhealth-careworkers.

Implementing these practices can reduce the transmission of drug-resistantpathogens.However,nosinglepracticealonecanpreventorcontain theemergenceandprogressionofresistantmicroorganisms.Thus,amulticomponentapproachthatencompassesalllevelsofIPCinthehospitalandcommunitysettingisneeded.

3.3.3 WHO guidance on infection prevention and controlThe primary purpose of IPC inHCFs is to reduce the burden ofHAIs in patients,health workers, visitors and other people associated with HCFs. HAIs can beendemic,epidemic(withinthepopulationoftheHCF)orcanoccurasaconsequenceof transmission of a community-acquired infection to patients inHCFs, leading toamplificationoranepidemicofcommunity-acquiredinfections.

In 2014, the WHO Strategic and Technical Advisory Group for addressing AMRestablishedasetoffourbasicIPCguidelinesspecifictothecontainmentofAMR(47):

1. Standard precautions a.Handhygiene b.Sterilizationanddisinfectionofmedicalmaterials c.Preventionandmanagementofinjuriesfromsharpinstruments2. Early detection of disease and isolation precautions a.Patientdisplacement b.Useofpersonalprotectiveequipment3. Aseptic technique and device management for clinical procedures, according to

the scope of care4. Waste management.

Theseguidelinesarebasicandindispensable.TheirinclusioninIPCprogrammescancontainHAIs and the spread of antimicrobial-resistant pathogens. To complywiththeWHO-recommendedIPCguidelines,surveillancesystemsneedtobeinplaceforHAIsandfor theassessmentofcompliancewith IPCguidelinesandpractices.This



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informationalsodirectlycontributes toassessingthe impactof IPCinterventions inreducingandcontainingthespreadofHAIs,inparticular,AMR. (25)

Inaddition to theWHOIPCguidelines, theRegionalOffice for theWesternPacifichasbeensupportingIPCcapacity-buildingthroughtheonlinelearningviathePacificOpenLearningHealthNet(POLHN)inpartnershipwithPacificministriesofhealth. (48)Todate,thereare38POLHNlearningcentreslocatedin12countries:CookIslands,theFederatedStatesofMicronesia,Fiji,Kiribati, theMarshall Islands,Nauru,Palau,Samoa,SolomonIslands,Tonga,TuvaluandVanuatu.AsofJanuary2015,morethan180 Pacific healthworkers had enrolled in POLHN’s online IPC coursewhichwaslaunchedinearly2014.

3.3.4 National coordinated IPC programmes and networksThere is urgent need for a system-wide approach to integrate AMR control intonationalIPCpoliciesandpracticesinHCFs.AMRcomponentsmustbeincorporatedinto all areas of HCF operations. To coordinate national IPC programmes andnetworks,anationaladvisorycommitteeshouldbesetuptodesignandmonitortheimplementation of effective IPC policies. (49) The IPC advisory committee shouldconsist of experienced and knowledgeable members who can provide evidence-based advice and support. However, hospital directors should ultimately takefull responsibility for IPC. Adequate financial support is also needed to maintainnational IPC activities and support IPC implementation in HCFs. The committeeshoulddevelopandregularlyupdatenationalIPCguidelinesforastreamlinedeffortto contain HAIs andAMR in HCFs throughout the country. The inclusion of IPCindicatorsandpractices in thenationalhospitalaccreditationsystemwould furtherenhance IPC activities.

TheprogressofIPCprogrammesshouldalsobemeasured.Indicatorsofprogresscaninclude regularmonitoring of compliance rates of hand hygiene and consumptionof alcohol-based hand rubs. Other indicators include the continued monitoring ofimportant pathogens that cause HAIs through surveillance. These include MRSA,extended-spectrum beta-lactamase-producing Enterobacteriaceae and carbapenem-resistantEnterobacteriaceae,allofwhichposeserioushealth threats inhospitalandcommunitysettings.



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