革兰阳性球菌耐药与治疗课件

革兰阳性球菌耐药与治疗倪语星上海交通大学医学院附属瑞金医院革兰阳性球菌耐药与治疗倪语星1革兰阳性球菌耐药与治疗课件2MDR细菌已成为全球关注的焦点在全球范围内，“ESKAPE”耐药已成为导致患者发病及死亡的重要原因1“ESKAPE”耐药现象日益严重，但当前新型抗菌药物的研发逐渐减缓，未来可能面临无药可用的局面3新药数量1983-19871988-19921993-19971998-20022003-20071.RiceLBetal.TheJournalofInfectiousDiseases2008;197:1079–812./world-health-day/zh/3.BoucherHWetal.ClinicalInfectiousDiseases2009;48:1–12MDR细菌已成为全球关注的焦点在全球范围内，“ESKAPE”3我国主要的MDR致病菌我国，“ESKAPE”耐药菌株检出率高检出率(%)产ESBL大肠埃希菌MRSA产ESBL肺炎克雷伯菌属不动杆菌属*铜绿假单胞菌*耐万古霉素屎肠球菌*在G-菌中的检出率朱德妹等.中国感染与化疗杂志.2011;11(5):321-329我国主要的MDR致病菌我国，“ESKAPE”耐药菌株检出率高413967株5380株431株1733株1623株呼吸道尿液粪便伤口分泌物血液克雷伯菌属15.3%大肠埃希菌47.1%金葡菌22.7%凝(-)葡萄球菌50.2%志贺菌属80.7%金葡菌14.7%肠球菌21.0%大肠埃希菌16.7%大肠埃希菌11.5%不动杆菌12.8%克雷伯菌8.2%铜绿假单孢菌9.5%金葡菌7.7%铜绿假单胞菌11.4%凝(-)葡萄球菌5.8%克雷伯菌

8.9%克雷伯菌5.7%汪复,等.中国感染与化疗杂志.2010;10(5):325-334.各类标本中的主要病原菌？13967株5380株431株1733株1623株呼吸道尿5血培养排名前10位的临床致病菌细菌名称正确污染率不确定金葡大肠埃希菌99.30.00.7凝固酶阴性葡萄球菌12.481.95.8肺克100.00.00.0肠球菌69.916.114.0绿脓肺链100.00.00.0白念90.00.010.0草绿链38.049.312.7阴沟100.00.00.0血培养排名前10位的临床致病菌细菌名称正确污染率不确定金葡86一、药敏监测数据一、药敏监测数据7R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.R.N.Jonesetal.Diagnostic8ZAAPS监测项目简介

时间入选情况G+菌株2006年16个国家的50所医学研究中心共分离到4216株G+菌2007年23个国家的64所医学研究中心共分离到5591株G+菌R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.近6年ZAAPS监测共分离到G+菌34170株ZAAPS监测项目简介时间入选情况G+菌株2006年16个9不同国家MRSA耐药率加拿大：55.7%拉丁美洲：平均为50.1%(29.0%-64.1%)欧洲：平均为28.2%(1.7%-56.2%)亚太地区：平均为44.2%(25.3%-68.0%)R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.不同国家MRSA耐药率加拿大：55.7%R.N.Jones10常用抗菌药物对金黄色葡萄球菌抗菌活性金黄色葡萄球菌(3000)MIC(μg/mL)百分比(%)50%90%范围敏感/耐药利奈唑胺220.25-8>99.9/—环丙沙星0.5>40.06->464.2/34.9左氧氟沙星≤0.5>4≤0.5->465.2/34.6克林霉素≤0.25>2≤0.25->274.3/25.6替考拉宁≤2≤2≤2-8100.0/0.0TMP-SMX≤0.5≤0.5≤0.5->293.1/6.9万古霉素110.25-2100.0/0.0R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.2007年ZAAPS项目对3000株金黄色葡萄球菌药敏监测结果常用抗菌药物对金黄色葡萄球菌抗菌活性金黄色葡萄球菌(300011常用抗菌药物对CoNS的抗菌活性CoNS(716)MIC(μg/mL)百分比(%)50%90%范围敏感/耐药利奈唑胺11≤0.06-899.7/—青霉素>2>2≤0.25->220.4/79.6奎奴普丁-达托普丁≤0.250.5≤0.25->298.9/0.6替考拉宁≤28≤2->1697.5/0.3万古霉素12≤0.12-899.0/0.0R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.2007年ZAAPS项目对716株CoNS药敏监测结果常用抗菌药物对CoNS的抗菌活性CoNS(716)MIC(μ122008年CHINET监测网各医院金葡菌MR菌株检出率医院金黄色葡萄球菌医院金黄色葡萄球菌MR株数/总株数（%）MR株数/总株数（%）华山医院421/54377.5北京医院/214/279/76.7瑞金医院375/56666.3上海儿科医院/43/291/14.8协和医院221/38058.7上海儿童医院/68/353/20.4同济医院257/41762.6重庆医大一附院/8/18/44.4浙医一附院107/21450.0甘肃省人民医院/58/112/51.8广州一附院79/12065.8新疆医大一附院/65/146/44.5总计1916/343955.7(14.8-77.5)两家儿童医院MRSA检出率低2008年CHINET监测网各医院金葡菌MR菌株检出率医院金132008年CHINET监测网各医院凝固酶(-)葡萄球菌MR菌株检出率医院凝固酶阴性葡萄球菌医院凝固酶阴性葡萄球菌MR株数/总株数（%）MR株数/总株数（%）华山医院45/5188.2北京医院12/1675.0瑞金医院90/12174.4上海儿科医院/304/503/60.4协和医院186/22881.6上海儿童医院/302/327/92.4同济医院172/21181.5重庆医大一附院/1/1//浙医一附院560/74775.0甘肃省人民医院/20/28/71.4广州一附院36/4481.8新疆医大一附院/16/21/76.2总计1744/229875.9(60.4-92.4)2008年CHINET监测网各医院凝固酶(-)葡萄球菌MR菌14MSSA(1495株)与MRSA(1916株)的耐药率（%）MRSA的耐药率>MSSA仍有75％，67％菌株对SMZ/TMP、磷霉素敏感MSSA对β内酰胺类、氟喹诺酮类、SMZ/TMP、利福平、磷霉素的耐药率<10％无万古、替考拉宁、利奈唑胺耐药株MSSA(1495株)与MRSA(1916株)的耐药率（%）15MSCNS(555株)和MRCNS(1723株)的耐药率（%）MRCNS的耐药率>MSCNSMRCNS耐药率<MRSA,但对SMZ/TMP耐药率>MRSA，但仍有约90％、65％菌株对利福平、磷霉素敏感。无万古、替考拉宁、利奈唑胺耐药株MSCNS(555株)和MRCNS(1723株)的耐药率（%16革兰阳性球菌耐药与治疗课件17革兰阳性球菌耐药与治疗课件18革兰阳性球菌耐药与治疗课件19革兰阳性球菌耐药与治疗课件20[2006-2010年监测数据]

耐万古霉素的粪肠球菌与屎肠球菌发生率极少细菌耐药率(%)20061CHINET(N=2621)20072CHINET(N=2634)20084CHINET(N=2859)2006-20073MOH(N=7528)20095CHINET(N=3369)20106CHINET(N=3646)汪复.2006年中国CHINET细菌耐药性监测.中国感染与化疗杂志2008;8(1):1-9.汪复等.2007年中国CHINET细菌耐药性监测.中国感染与化疗杂志2008;8(5):325-333.肖永红等.2006-2007年Mohnarin细菌耐药检测.中华医院感染学杂志2008;18(8):1051-1056.汪复等.2008年中国CHINET细菌耐药性监测.中国感染与化疗杂志2009;9(5):321-329.

汪复等.2009年中国CHINET细菌耐药性监测.中国感染与化疗杂志2010;10(5):325-334.朱德妹,汪复,胡付品等.2010年中国CHINET细菌耐药性监测.中国感染与化疗杂志2011;11(5):321-329.[2006-2010年监测数据]

耐万古霉素的粪肠球菌与屎21二、S.aureusandMRSAMethicillinresistantS.aureusPresenceofamecAgeneCarriedinamobilegeneticelement(SCCmec)Mostroutinetesting–antibioticsensitivity(MRSAidagar)二、S.aureusandMRSAMethicilli22LGA251MSSALGA251MSSA23革兰阳性球菌耐药与治疗课件24革兰阳性球菌耐药与治疗课件25CLSI药敏指南 “金黄色葡萄球菌或所有凝固酶阴性葡萄球菌如对苯唑西林(或甲氧西林)耐药，则对青霉素类、头孢菌素类、碳青霉烯类和含酶抑制剂的复方制剂均应报告耐药，而不考虑其体外药敏结果”。CLSI药敏指南 “金黄色葡萄球菌或所有凝固酶阴性葡萄球菌26CefoxitinDiskTestformecA-mediatedResistanceinStaphylococciBreakpoints(mm)OrganismOldM100-S16New

M100-S17ResSuscResSuscS.aureusS.lugdunensis192021*22**CoNSNochange24252425*Reportasoxacillinresistant**ReportasoxacillinsusceptibleCoNS,coagulase-negativestaphylococciOX-R=mecA=MRSA?CefoxitinDiskTestformecA-m27革兰阳性球菌耐药与治疗课件28DiscoveryofthenewMRSAstrains(LGA251)WefoundS.aureusthatwerehighlyresistantononefarm(ST425) (OxacilinMIC=16mg/l,cefoxitinMIC=32mg/l)LookedformecAgene–negativeresultsSequencedwholegenometolookforthereasonFoundadivergentmecAgeneinsideanewSCCmecDiscoveryofthenewMRSAstra29ImportanceofthenewMRSAMoleculartests(PCR&slideagglutinationtest)designedtodetectMRSAgiveanegativeresultwhentestedonthenewstrainThenewMRSAismovingbetweenpeopleandcattleOldMRSAwasnotfoundindairycowsDivergentMRSAisfoundinS.aureusstrainsthoughttoberestrictedtoanimalsGeographicalclusteringofhumanandcowstrainsofthenewMRSADivergentMRSAmecAgenehasnotbeenfoundinhumanstrainsIsolationsofdivergentMRSAappeartobeincreasingImportanceofthenewMRSAMole30NewMRSAisolatesbyyear0102030405060ScotlandEnglandDenmark1975200220042005200620072008200920102011NewMRSAisolatesbyyear0102031CC130CC599ST425CC1943ST1021CC49HumanCattleSheepRatCatDogHorseGPigDeerSealFinchRabbitCC130CC599ST425CC1943ST1021CC432三、对糖肽类的耐药机制三、对糖肽类的耐药机制33VRSAvanAgenepositiveChangeofD-alanyl-D-alanyl-D-lactate1000folddecreaseinaffinitytovancomycinTypicalMIC>16mg/LtovancomycinVRSAvanAgenepositive34VRSAUSA–12cases/HAI/settings/lab/vrsa_lab_search_containment.htmlFirstdiscoveredin20028fromMichigan!2mostreccentfromDelaware(2010)Iran-1caseTHE-2,2005India–6casesFromintensivecareunitsin2tertiaryhospitalsinHydrabad-2008VRSAUSA–12cases35VISAisolatesNotasinglemutationoracquisitionofasinglegeneComplex!Involvesaseriesofchanges!Increasedcellwallthickening,increasednumberoffreeD-alanyl-D-alaninresidues,reducedautolyticactivity,mutationsinregulatorsofcellwallsynthesis(i.e.graRS,vraSR),changeintranscriptionprofileTypicalMIC4-8mg/LVISAisolatesNotasinglemuta36hVISAisolatessusceptiblebystandardMICtestingbuthavesubpopulationsexpressingreducedsusceptibilitySametypesofresistancemechanismsasVISAisolatesTypicalMIC1-2mg/LPopulationprofileofinitialisolate(6000)andafterpersistantbacteremia/vancomycintherapy(6001)Howden,AAC,2006JKD6001JKD6000ATCC25923Mu3987654321012345678Vancomycinμg/mlLog10CFU/mlhVISAisolatessusceptiblebys37PrevalenceofVISA/hVISAHighlyvariableprevalence’sarereportedintheliteratureincludingwithincountriesIllustratedbydatafromAustraliaMelbourne(Austin)–117MRSAVISA2isolates(2%)Sydney401MRSABSIhVISA46(11.5%)(almostallST239)VISA2(0.5%)Australia–general–532SAB/202MRSAhVISA2isolates0.4%/1%VISA0isolatesHorneAAC,2009.ValHal,Plosone.Homes,JID2011.PrevalenceofVISA/hVISAHighly38SummaryTheprevalenceofVRSAandVISAisolatesarestilllowinmostpartoftheworldTheprevalanceofhVISAvariesingeneralrelativelylowbutcanlocallybeup50%ofMRSAisolatesThereareincreasingevidencethatstrainswithMIC>1mg/Lareassociatedwithpooeroutcome–butlargedefinitiveprospectivestudiesisneededSummaryTheprevalenceofVRSA39Linezolid-RS.aureus:ReviewApril–June200812patientswithLRSA6VAP,3bacteremia1predominantclonecfrmediatedresistanceHealthcareworkersandenvironmentNegClinicalOutbreakofLinezolid-ResistantStaphylococcusaureusinanIntensiveCareUnitSanchezM,JAMA2010Linezolid-RS.aureus:ReviewAp40Linezolid-RS.aureusoutbreakK-217ClinicalandMicrobiologicalcharacteristicsofLinezolid-ResistantStaphylococcusaureus(LRSA)April-June2008FromJuly2001toMay2011:22publications,77patientsMechanismofresistancewasaRNAmutationin37cfrgenein33Both1Notreported730ICU-patients,17patientsonhospitalwordsand18outpatientsLRSAcaused29respiratorytractinfections,mostlyVAP,bacteremiain7,andSSTIin6.Sixpatientswerecolonized.MdelaTorre,ICAAC,Chicagao2011Linezolid-RS.aureusoutbreak41MechanismsofLinezolidResistanceBindingtothePetidylTransferaseCenter(PTC)ontheribosomeMutationsof23SrRNARibosomalproteinsL3andL4CfrmethyltransferasegeneLongKS.AAC2012.ResistancetoLinezolidCausedbymodificationsatItsBindingSiteontheRibosomeMechanismsofLinezolidResist42LR-MRSAoutbreak:ResultsAllLR-MRSA(patientsandHCW’s)weregenotypicallyidenticalbyPFGEThecfrgenewasdetectedinallisolatesNoneoftheisolatesshowedmutationsinthe235rRNAsubunitLR-MRSAoutbreak:ResultsAllL43LR-MRSAoutbreak:LinezolidUse05101520251601401201008060402002009JanuaryFebruaryMarchAprilMayJuneJulyAugustSeptemberOctoberNovemberDecemberJanuaryFebruaryMarchAprilMayJuneLR-MRSAMRSADDDsLinezolidIncidencedensityNpatientsandincidencedensityMRSAinPSICULR-MRSAoutbreak:LinezolidUs44Dapto-Resistance:mechanismsMutationsingenesessentialforMembranephospholipidbiosynthesisreducethenet-negativechargeofthecellmembrane.ElectrorepulsionofDaptomycinWholeGenomeCharacterizationoftheMechanismsofDaptomycinResistanceinClinicalandLaboratoryDerivedIsolatesofStaphylococcusaureusPelegAY.PLoSone2012.Dapto-Resistance:mechanismsMu45Dapto-Resistance:mechanismsCorrelationbetweennonsusceptibilitytodaptomycinisduetocellwallthickeningPelegAY.PLoSone2012.Dapto-Resistance:mechanismsCo46DaptomycinMICincreaseamongpatientswithmethicillin-resistantStaphylococcusaureuspersistentbacteraemiatreatedwithdaptomycin.Prospectivestudyin22Spanishhospitals.O.Gasch*,M.Camoez,MA.Dominguez,B.Padilla…IncreaseinMIC’sinsequentialisolatesbothtoDaptomycinandVancomycin.SwitchtoanotherdrugifBC’sdonotbecomenegativeGashO.ECCMID2012.DaptomycinMICincreaseamong47四、VRE肠球菌对万古霉素的耐药可分为低水平耐药（MIC，8-32mg/L）和高水平耐药（MIC，≥64mg/L）。根据肠球菌对万古霉素和替考拉宁的不同耐药水平及耐药基因，VRE分为四个表型，分别是VanA，VanB，VanC和VanD。

四、VRE肠球菌对万古霉素的耐药可分为低水平耐药（MIC，848VRE的分型及其耐药表型

类型万古霉素（μg/ml）替考拉宁

VanA64~＞100016~512VanB4~10240.25~2VanC2~320.12~2VanD16~642~4CLSIbp≤2,4-816≤8,16≥32VRE的分型及其耐药表型类型49chromIDVRE粪肠球菌屎肠球菌chromIDVRE粪肠球菌屎肠球菌50VRE筛选试验阳性必须做MIC确认，并观察动力和色素鉴别菌种，以区分获得性耐药（VanA和VanB）及某些菌种存在的固有的中介（8-16）耐药（VanC），后者在感染控制中的意义与VRE不同。

VRE筛选试验阳性必须做MIC确认，并观察动力和色素鉴别菌种51肠球菌的治疗粪肠球菌：氨苄西林加减庆大霉素重症，HLAR：万古霉素屎肠球菌：庆大霉素重症，HLAR：万古霉素VRE：VanA：替考拉宁，其他：利奈唑胺泌尿道感染：呋喃妥因肠球菌的治疗粪肠球菌：氨苄西林加减庆大霉素52五、经验治疗五、经验治疗53以下情况高度提示革兰阳性球菌感染血流感染，包括导管相关的血流感染，菌血症，脓毒症，细菌性心内膜炎皮肤软组织感染，包括伤口和创面感染手术部位感染，包括植入物感染骨和关节感染，骨髓炎以下情况高度提示革兰阳性球菌感染54以下情况有可能革兰阳性球菌感染HAP（MRSA）VAP（MRSA）复杂UTI（MRSA，肠球菌）以下情况有可能革兰阳性球菌感染55革兰阳性球菌感染？葡萄球菌占革兰阳性球菌感染第一位金黄色葡萄球菌占葡萄球菌感染第一位MRSA占金黄色葡萄球菌50~60%革兰阳性球菌感染？葡萄球菌占革兰阳性球菌感染第一位56以下情况考虑糖肽类治疗脓毒症骨、关节感染手术部位感染血流感染：菌血症、心内膜炎导管相关感染院内肺炎复杂性尿路感染以下情况考虑糖肽类治疗脓毒症57ThankYou!ThankYou!58革兰阳性球菌耐药与治疗倪语星上海交通大学医学院附属瑞金医院革兰阳性球菌耐药与治疗倪语星59革兰阳性球菌耐药与治疗课件60MDR细菌已成为全球关注的焦点在全球范围内，“ESKAPE”耐药已成为导致患者发病及死亡的重要原因1“ESKAPE”耐药现象日益严重，但当前新型抗菌药物的研发逐渐减缓，未来可能面临无药可用的局面3新药数量1983-19871988-19921993-19971998-20022003-20071.RiceLBetal.TheJournalofInfectiousDiseases2008;197:1079–812./world-health-day/zh/3.BoucherHWetal.ClinicalInfectiousDiseases2009;48:1–12MDR细菌已成为全球关注的焦点在全球范围内，“ESKAPE”61我国主要的MDR致病菌我国，“ESKAPE”耐药菌株检出率高检出率(%)产ESBL大肠埃希菌MRSA产ESBL肺炎克雷伯菌属不动杆菌属*铜绿假单胞菌*耐万古霉素屎肠球菌*在G-菌中的检出率朱德妹等.中国感染与化疗杂志.2011;11(5):321-329我国主要的MDR致病菌我国，“ESKAPE”耐药菌株检出率高6213967株5380株431株1733株1623株呼吸道尿液粪便伤口分泌物血液克雷伯菌属15.3%大肠埃希菌47.1%金葡菌22.7%凝(-)葡萄球菌50.2%志贺菌属80.7%金葡菌14.7%肠球菌21.0%大肠埃希菌16.7%大肠埃希菌11.5%不动杆菌12.8%克雷伯菌8.2%铜绿假单孢菌9.5%金葡菌7.7%铜绿假单胞菌11.4%凝(-)葡萄球菌5.8%克雷伯菌

8.9%克雷伯菌5.7%汪复,等.中国感染与化疗杂志.2010;10(5):325-334.各类标本中的主要病原菌？13967株5380株431株1733株1623株呼吸道尿63血培养排名前10位的临床致病菌细菌名称正确污染率不确定金葡大肠埃希菌99.30.00.7凝固酶阴性葡萄球菌12.481.95.8肺克100.00.00.0肠球菌69.916.114.0绿脓肺链100.00.00.0白念90.00.010.0草绿链38.049.312.7阴沟100.00.00.0血培养排名前10位的临床致病菌细菌名称正确污染率不确定金葡864一、药敏监测数据一、药敏监测数据65R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.R.N.Jonesetal.Diagnostic66ZAAPS监测项目简介

时间入选情况G+菌株2006年16个国家的50所医学研究中心共分离到4216株G+菌2007年23个国家的64所医学研究中心共分离到5591株G+菌R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.近6年ZAAPS监测共分离到G+菌34170株ZAAPS监测项目简介时间入选情况G+菌株2006年16个67不同国家MRSA耐药率加拿大：55.7%拉丁美洲：平均为50.1%(29.0%-64.1%)欧洲：平均为28.2%(1.7%-56.2%)亚太地区：平均为44.2%(25.3%-68.0%)R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.不同国家MRSA耐药率加拿大：55.7%R.N.Jones68常用抗菌药物对金黄色葡萄球菌抗菌活性金黄色葡萄球菌(3000)MIC(μg/mL)百分比(%)50%90%范围敏感/耐药利奈唑胺220.25-8>99.9/—环丙沙星0.5>40.06->464.2/34.9左氧氟沙星≤0.5>4≤0.5->465.2/34.6克林霉素≤0.25>2≤0.25->274.3/25.6替考拉宁≤2≤2≤2-8100.0/0.0TMP-SMX≤0.5≤0.5≤0.5->293.1/6.9万古霉素110.25-2100.0/0.0R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.2007年ZAAPS项目对3000株金黄色葡萄球菌药敏监测结果常用抗菌药物对金黄色葡萄球菌抗菌活性金黄色葡萄球菌(300069常用抗菌药物对CoNS的抗菌活性CoNS(716)MIC(μg/mL)百分比(%)50%90%范围敏感/耐药利奈唑胺11≤0.06-899.7/—青霉素>2>2≤0.25->220.4/79.6奎奴普丁-达托普丁≤0.250.5≤0.25->298.9/0.6替考拉宁≤28≤2->1697.5/0.3万古霉素12≤0.12-899.0/0.0R.N.Jonesetal.DiagnosticMicrobiologyandInfectiousDisease.2009;64:191–201.2007年ZAAPS项目对716株CoNS药敏监测结果常用抗菌药物对CoNS的抗菌活性CoNS(716)MIC(μ702008年CHINET监测网各医院金葡菌MR菌株检出率医院金黄色葡萄球菌医院金黄色葡萄球菌MR株数/总株数（%）MR株数/总株数（%）华山医院421/54377.5北京医院/214/279/76.7瑞金医院375/56666.3上海儿科医院/43/291/14.8协和医院221/38058.7上海儿童医院/68/353/20.4同济医院257/41762.6重庆医大一附院/8/18/44.4浙医一附院107/21450.0甘肃省人民医院/58/112/51.8广州一附院79/12065.8新疆医大一附院/65/146/44.5总计1916/343955.7(14.8-77.5)两家儿童医院MRSA检出率低2008年CHINET监测网各医院金葡菌MR菌株检出率医院金712008年CHINET监测网各医院凝固酶(-)葡萄球菌MR菌株检出率医院凝固酶阴性葡萄球菌医院凝固酶阴性葡萄球菌MR株数/总株数（%）MR株数/总株数（%）华山医院45/5188.2北京医院12/1675.0瑞金医院90/12174.4上海儿科医院/304/503/60.4协和医院186/22881.6上海儿童医院/302/327/92.4同济医院172/21181.5重庆医大一附院/1/1//浙医一附院560/74775.0甘肃省人民医院/20/28/71.4广州一附院36/4481.8新疆医大一附院/16/21/76.2总计1744/229875.9(60.4-92.4)2008年CHINET监测网各医院凝固酶(-)葡萄球菌MR菌72MSSA(1495株)与MRSA(1916株)的耐药率（%）MRSA的耐药率>MSSA仍有75％，67％菌株对SMZ/TMP、磷霉素敏感MSSA对β内酰胺类、氟喹诺酮类、SMZ/TMP、利福平、磷霉素的耐药率<10％无万古、替考拉宁、利奈唑胺耐药株MSSA(1495株)与MRSA(1916株)的耐药率（%）73MSCNS(555株)和MRCNS(1723株)的耐药率（%）MRCNS的耐药率>MSCNSMRCNS耐药率<MRSA,但对SMZ/TMP耐药率>MRSA，但仍有约90％、65％菌株对利福平、磷霉素敏感。无万古、替考拉宁、利奈唑胺耐药株MSCNS(555株)和MRCNS(1723株)的耐药率（%74革兰阳性球菌耐药与治疗课件75革兰阳性球菌耐药与治疗课件76革兰阳性球菌耐药与治疗课件77革兰阳性球菌耐药与治疗课件78[2006-2010年监测数据]

耐万古霉素的粪肠球菌与屎肠球菌发生率极少细菌耐药率(%)20061CHINET(N=2621)20072CHINET(N=2634)20084CHINET(N=2859)2006-20073MOH(N=7528)20095CHINET(N=3369)20106CHINET(N=3646)汪复.2006年中国CHINET细菌耐药性监测.中国感染与化疗杂志2008;8(1):1-9.汪复等.2007年中国CHINET细菌耐药性监测.中国感染与化疗杂志2008;8(5):325-333.肖永红等.2006-2007年Mohnarin细菌耐药检测.中华医院感染学杂志2008;18(8):1051-1056.汪复等.2008年中国CHINET细菌耐药性监测.中国感染与化疗杂志2009;9(5):321-329.

汪复等.2009年中国CHINET细菌耐药性监测.中国感染与化疗杂志2010;10(5):325-334.朱德妹,汪复,胡付品等.2010年中国CHINET细菌耐药性监测.中国感染与化疗杂志2011;11(5):321-329.[2006-2010年监测数据]

耐万古霉素的粪肠球菌与屎79二、S.aureusandMRSAMethicillinresistantS.aureusPresenceofamecAgeneCarriedinamobilegeneticelement(SCCmec)Mostroutinetesting–antibioticsensitivity(MRSAidagar)二、S.aureusandMRSAMethicilli80LGA251MSSALGA251MSSA81革兰阳性球菌耐药与治疗课件82革兰阳性球菌耐药与治疗课件83CLSI药敏指南 “金黄色葡萄球菌或所有凝固酶阴性葡萄球菌如对苯唑西林(或甲氧西林)耐药，则对青霉素类、头孢菌素类、碳青霉烯类和含酶抑制剂的复方制剂均应报告耐药，而不考虑其体外药敏结果”。CLSI药敏指南 “金黄色葡萄球菌或所有凝固酶阴性葡萄球菌84CefoxitinDiskTestformecA-mediatedResistanceinStaphylococciBreakpoints(mm)OrganismOldM100-S16New

M100-S17ResSuscResSuscS.aureusS.lugdunensis192021*22**CoNSNochange24252425*Reportasoxacillinresistant**ReportasoxacillinsusceptibleCoNS,coagulase-negativestaphylococciOX-R=mecA=MRSA?CefoxitinDiskTestformecA-m85革兰阳性球菌耐药与治疗课件86DiscoveryofthenewMRSAstrains(LGA251)WefoundS.aureusthatwerehighlyresistantononefarm(ST425) (OxacilinMIC=16mg/l,cefoxitinMIC=32mg/l)LookedformecAgene–negativeresultsSequencedwholegenometolookforthereasonFoundadivergentmecAgeneinsideanewSCCmecDiscoveryofthenewMRSAstra87ImportanceofthenewMRSAMoleculartests(PCR&slideagglutinationtest)designedtodetectMRSAgiveanegativeresultwhentestedonthenewstrainThenewMRSAismovingbetweenpeopleandcattleOldMRSAwasnotfoundindairycowsDivergentMRSAisfoundinS.aureusstrainsthoughttoberestrictedtoanimalsGeographicalclusteringofhumanandcowstrainsofthenewMRSADivergentMRSAmecAgenehasnotbeenfoundinhumanstrainsIsolationsofdivergentMRSAappeartobeincreasingImportanceofthenewMRSAMole88NewMRSAisolatesbyyear0102030405060ScotlandEnglandDenmark1975200220042005200620072008200920102011NewMRSAisolatesbyyear0102089CC130CC599ST425CC1943ST1021CC49HumanCattleSheepRatCatDogHorseGPigDeerSealFinchRabbitCC130CC599ST425CC1943ST1021CC490三、对糖肽类的耐药机制三、对糖肽类的耐药机制91VRSAvanAgenepositiveChangeofD-alanyl-D-alanyl-D-lactate1000folddecreaseinaffinitytovancomycinTypicalMIC>16mg/LtovancomycinVRSAvanAgenepositive92VRSAUSA–12cases/HAI/settings/lab/vrsa_lab_search_containment.htmlFirstdiscoveredin20028fromMichigan!2mostreccentfromDelaware(2010)Iran-1caseTHE-2,2005India–6casesFromintensivecareunitsin2tertiaryhospitalsinHydrabad-2008VRSAUSA–12cases93VISAisolatesNotasinglemutationoracquisitionofasinglegeneComplex!Involvesaseriesofchanges!Increasedcellwallthickening,increasednumberoffreeD-alanyl-D-alaninresidues,reducedautolyticactivity,mutationsinregulatorsofcellwallsynthesis(i.e.graRS,vraSR),changeintranscriptionprofileTypicalMIC4-8mg/LVISAisolatesNotasinglemuta94hVISAisolatessusceptiblebystandardMICtestingbuthavesubpopulationsexpressingreducedsusceptibilitySametypesofresistancemechanismsasVISAisolatesTypicalMIC1-2mg/LPopulationprofileofinitialisolate(6000)andafterpersistantbacteremia/vancomycintherapy(6001)Howden,AAC,2006JKD6001JKD6000ATCC25923Mu3987654321012345678Vancomycinμg/mlLog10CFU/mlhVISAisolatessusceptiblebys95PrevalenceofVISA/hVISAHighlyvariableprevalence’sarereportedintheliteratureincludingwithincountriesIllustratedbydatafromAustraliaMelbourne(Austin)–117MRSAVISA2isolates(2%)Sydney401MRSABSIhVISA46(11.5%)(almostallST239)VISA2(0.5%)Australia–general–532SAB/202MRSAhVISA2isolates0.4%/1%VISA0isolatesHorneAAC,2009.ValHal,Plosone.Homes,JID2011.PrevalenceofVISA/hVISAHighly96SummaryTheprevalenceofVRSAandVISAisolatesarestilllowinmostpartoftheworldTheprevalanceofhVISAvariesingeneralrelativelylowbutcanlocallybeup50%ofMRSAisolatesThereareincreasingevidencethatstrainswithMIC>1mg/Lareassociatedwithpooeroutcome–butlargedefinitiveprospectivestudiesisneededSummaryTheprevalenceofVRSA97Linezolid-RS.aureus:ReviewApril–June200812patientswithLRSA6VAP,3bacteremia1predominantclonecfrmediatedresistanceHealthcareworkersandenvironmentNegClinicalOutbreakofLinezolid-ResistantStaphylococcusaureusinanIntensiveCareUnitSanchezM,JAMA2010Linezolid-RS.aureus:ReviewAp98Linezolid-RS.aureusoutbreakK-217ClinicalandMicrobiologicalcharacteristicsofLinezolid-ResistantStaphylococcusaureus(LRSA)April-June2008FromJuly2001toMay2011:22publications,77patientsMechanismofresistancewasaRNAmutationin37cfrgenein33Both1Notreported730ICU-patients,17patientsonhospitalwordsand18outpatientsLRSAcaused29respiratorytractinfections,mostlyVAP,bacteremiain7,andSSTIin6.Sixpatientswerecolonized.MdelaTorre,ICAAC,Chicagao2011Linezolid-RS.aureusoutbreak99MechanismsofLinezolidResistanceBindingtothePetidylTransferaseCenter(PTC)ontheribosomeMutationsof23SrRNARibosomalproteinsL3andL4CfrmethyltransferasegeneLongKS.AAC2012.ResistancetoLinezolidCausedbymodificationsatItsBindingSiteontheRibosomeMechanismsofLinezolidResist100LR-MRSAoutbreak:ResultsAllLR-MRSA(patientsandHCW’s)weregenotypicallyidenticalbyPFGEThecfrgenewasdetectedinallisolatesNoneoftheisolatesshowedmutationsinthe235rRNAsubunitLR-MRSAoutbreak:ResultsAllL101LR-MRSAoutbreak:LinezolidUse05101520251601401201008060402002009JanuaryFeb