中国细菌耐药性现状英文版.pptx

Bacterial Resistance in China Minggui Wang,M.D.Minggui Wang,M.D.Institute of AntibioticsInstitute of AntibioticsHuashan Hospital,Fudan UniversityHuashan Hospital,Fudan UniversityOutlineAntimicrobial Resistance and Its MechanismsAntimicrobial Resistance and Its Mechanismsn nGram-positive cocciGram-positive cocci Streptococcus pneumoniaeStreptococcus pneumoniae Staphylococcus spp.Staphylococcus spp.n nGram-negative bacilliGram-negative bacilli EnterobacteriaceaeEnterobacteriaceaen nEscherichia coliEscherichia colin nKlebsiella spp.Klebsiella spp.n nEnterobacter sppEnterobacter spp.,et al.,et al.Non-fermenting gram-negative bacilli Non-fermenting gram-negative bacilli (non-fermenters)(non-fermenters)Antimicrobial Resistance inStreptococcus pneumoniaeHistory of studies on antimicrobial resistance on Streptococcus pneumoniae 19671970 1978 1980 1991 2001Spread around the world First case of PRSP First case of MDR Mechanism of PRSPRegional problemGlobal problem-lactams(penicillin)MacrolidesFluoroquinolonesPenicillin resistance in S.pneumoniae in China in late 1990YearYearRegionRegionPopulatiPopulationonSourceSourceNo.of No.of StrainsStrainsPNSSPPNSSP(%)(%)PISPPISP(%)(%)PRSPPRSP(%)(%)96-9996-99ShanghaiShanghaiAdultsAdultsClinicalClinical68683 33 30 0ChildrenChildrenClinicalClinical6060131313130 019981998ChildrenChildrenCarriageCarriage222222141414140 019981998GuangzhouGuangzhouClinicalClinical102102121212120 0ChildrenChildrenCarriageCarriage151151151515150 01997*1997*BejingBejingClinicalClinical7979141411112 2ChildrenChildrenCarriage Carriage 244244141413131 199-0099-004 centers4 centers ClinicalClinical553553141412122 2PNSSP,penicillin non-susceptible S.pneumoniae;PISP,penicillin intermediate S.pneumoniae;PRSP,penicillin resistant S.pneumoniae*AAC 1998;42:2633Penicillin resistance in S.pneumoniae in China in early 2000YearYearRegionRegionPopulatiPopulationonSourceSourceNo.of No.of StrainsStrainsPNSSPPNSSP(%)(%)PISPPISP(%)(%)PRSPPRSP(%)(%)20012001ShanghaiShanghaiChildrenChildrenClinical Clinical 100100555549496 601-0201-02BeijingBeijingShenyangShenyangClinicalClinical19219243433232111100-0200-023 centers3 centersChildrenChildrenClinicalClinical887887404034346 600-0100-014 centers4 centersChildrenChildrenClinical Clinical 624624414137374 4PNSSP,penicillin non-susceptible S.pneumoniae;PISP,penicillin intermediate S.pneumoniae;PRSP,penicillin resistant S.pneumoniaePenicillin resistance in S.pneumoniae has been increasing markedly since 2000Increasing trends of Penicillin resistance in S.pneumoniae in China Shanghai100 strains each yearBeijingMore than 100 strains each yearClinical strains isolated from Childrens HospitalReasons causing the rapid increasing of penicillin resistancen nThe increasing consumption of oral penicillins such as amoxicillinn nThe spead of resistant coloninesDifference of penicillin resistance in Difference of penicillin resistance in S.pneumoniaeS.pneumoniae isolated between adults and children isolated between adults and childrenYearYearRegionRegionPopulatiPopulationonSourceSourceNo.of No.of StrainsStrainsPNSSPPNSSP(%)(%)PISPPISP(%)(%)PRSPPRSP(%)(%)96-9996-99ShanghaiShanghaiAdultsAdultsClinicalClinical68683 33 30 0ChildrenChildrenClinicalClinical6060131313130 020042004ShanghaiShanghaiAdultsAdultsClinicalClinical34349 99 90 0ChildrenChildrenClinical Clinical 12412470704242282820042004Multiple Multiple centerscenters Adults AdultsClinicalClinical6969202017173 3PNSSP,penicillin non-susceptible S.pneumoniae;PISP,penicillin intermediate S.pneumoniae;PRSP,penicillin resistant S.pneumoniaeThe penicillin resistance rates were much higher in childrenThe penicillin resistance rates were much higher in childrenthan that in adultsthan that in adultsResistance of S.pneumoniae to macrolides 70%-90%of S.pneumoniae clinical isolates were resistant to erythromycinAntimicrobial resistance ofAntimicrobial resistance of S.pneumoniaeS.pneumoniae isolated from children isolated from children in Beijing,Shanghai,Guangzhou and Xiin Beijing,Shanghai,Guangzhou and Xi anan（2000200020012001）Mechanism of bacterial resistance:Mosaic PBP Genes in PRSPn nPenicillin resistance is due to alterations in endogenous PBPsDNA from related streptococci taken DNA from related streptococci taken up and incorporated into up and incorporated into S.S.pneumoniae pneumoniae genesgenesCzechoslovakia(1987)USA(1983)South Africa(1978)S SXN pen-sensitive S.pneumoniaeStreptococcus?PBP 2bMechanisms of resistance to macrolides(Wang M.Diagn Microbial Infect Dis 2001;39:187)(Wang M.Diagn Microbial Infect Dis 2001;39:187)n nTarget modification Phenotype cMLS,90%Phenotype cMLS,90%(159/176)(159/176)Phenotype iMLS,6%Phenotype iMLS,6%(10/176)(10/176)n nActive effluxPhenotype M Phenotype M 4%4%(7/176)(7/176)Antimicrobial Resistance inStaphylococcus spp.Trends of methicillin resistant Staphylococcus spp.(MRS)in China5%-24%35%-60%50%-70%Mechanism of MRSAn nMRSA contain novel PBP2a,substitutes for native PBPs;low affinity for all -lactamsn nPBP2a is encoded by mecA gene;expression controlled by mecI,mecR1 and other factorsSummaryAntimicrobial resistance in gram-positive coccinPenicillin resistance in S.pneumoniae has been increasing markedly since 2000 in ChinanThe resistance rates of S.pneumoniae to macrolides such as erythromycin are very highnMethicillin-resistant staphylococci are highly prevalentAntimicrobial Resistance inEnterobacteriaceaeAntimicrobial resistance rates of E.coli isolated in China in 2005(n=3758)Wang F.Chin J Infect Chemother 2006;6:289Wang F.Chin J Infect Chemother 2006;6:289Antimicrobial resistance rates of K.pneumoniae in China in 2005(n=2234)Wang F.Chin J Infect Chemother 2006;6:289Wang F.Chin J Infect Chemother 2006;6:289Extended-spectrum-lactamases(ESBLs)in Enterobacteriaceae in Chinan nESBL-producing strains ESBL-producing strains Hospital-acquired infectionsHospital-acquired infections1 1:n nE.coliE.coli,11-47%,11-47%n nK.pneumoniaeK.pneumoniae,14-51%,14-51%Community-acquired infectionsCommunity-acquired infections2 2:n nE.coliE.coli,16%,16%n nK.pneumoniaeK.pneumoniae,17%,17%n nThe main genotype of ESBLs is The main genotype of ESBLs is CTX-MCTX-M1 1,typically provides resistance to ceftaxime typically provides resistance to ceftaxime but often not to ceftazidime or aztreonambut often not to ceftazidime or aztreonam3 31,Xiong Z.Diagn Microbiol Infect Dis 2002;44:1952,Ling TK.AAC 2006;50:3743,Jacoby GA.Chin J Infect Chemother 2006;6:361Quinolone resistance rates in clinical isolates of E.coli in ShanghaiMechanisms involved in quinolone resistancen nAlterations in drug target enzymes(DNA gyrase and/or topoisomerase IV)n nAlterations in drug accumulation(active efflux system)Both result from chromosomal mutations Target modificationEffluxPlasmid-mediated quinolone resistance:qnr determinatsRSRRSRConjugationTransformationRqnrqnrA:Lancet,1998,the U.S.qnrB:AAC,2006,the U.S.qnrS:AAC,2005,JapanqnrC:7th NCCM,2007,ChinaPlasmid-mediated quinolone resistancen nqnr family:qnrA,qnrB,qnrS,qnrC Protection of quinolone targetsn naac(6)-Ib-cr(2006)aminoglycoside acetyltransferasen nqepA(2007)quinolone efflux pump SummaryAntimicrobial resistance in gram-negative bacillin nESBLs-producing strains of E.coli and K.pneumoniae are common,and spreading from hospital to communityn nQuinolone resistance rates in E.coli are especially highn nNew mechanisms of plasmid-mediated quinolone resistance emergedAntimicrobial Resistance inNon-fermenting gram-negative bacilli(non-fermenters)Importance of non-fermenters n nNon-fermenting gram-negative bacilli(non-Non-fermenting gram-negative bacilli(non-fermenters)include:fermenters)include:Pseudomonas aeruginosaPseudomonas aeruginosa AcinetobacterAcinetobacter spp.spp.Stenotrophomonas maltophiliaStenotrophomonas maltophilia AlcaligenesAlcaligenes spp.spp.BurkholderiaBurkholderia spp spp FlavobacteriumFlavobacterium(ChryseobateriumChryseobaterium)spp.,et al)spp.,et aln nNon-fermenters are highly resistant to Non-fermenters are highly resistant to commonly used antimicrobialscommonly used antimicrobialsn nThe infections of non-fermenters are difficult The infections of non-fermenters are difficult to treat with high mortalityto treat with high mortalityPercentage of non-fermenters in gram-negative bacilli in Shanghai hospitals(Wang F,et al.Int J Antimicrob Agents 2003;22:444)Wang F,et al.Int J Antimicrob Agents 2003;22:444)1460146016321632121512151171117113691369166116612028202830283028327532753005300552425242565656564818481858195819 56655665YearYearNo of strainsNo of strainsHigh incidence of non-fermenters in Gram-negative bacillin45%(6686/15244)of GNB were non-fermenters in CHINET(Resistance surveillance network in China)surveillance program in China in 2005 (Wang F.Chin J Infect Chemother 2006;6:289)nNon-fermenters increased from 41%in 1999 to 48%in 2001 in ICU clinical isolates of GNB in NPRS(Nosocomial Pathogens Resistance Surveillance)study program in China (Wang H,Chen MJ.Natl Med J China 2003;83:385)Resistance profile of 6123 strains of non-fermenters Resistance profile of 6123 strains of non-fermenters against 8 antimicrobials in CHINET in 2005against 8 antimicrobials in CHINET in 2005(Wang F.Chin J Infect Chemother 2006;6:289)(Wang F.Chin J Infect Chemother 2006;6:289)Antimicrobial agentsAntimicrobial agentsResistance Resistance rate(%)rate(%)Susceptibility Susceptibility rate(%)rate(%)CeftazidimeCeftazidime41415252CefepimeCefepime45454646Piperacillin-tazobactamPiperacillin-tazobactam44444949Cefoperazone-sulbactamCefoperazone-sulbactam23235252Imipenem Imipenem 43435454MeropenemMeropenem43435555CiprofloxacinCiprofloxacin41414848AmikacinAmikacin46464848Trends in antimicrobial resistance rates among strains Trends in antimicrobial resistance rates among strains of of P.aeruginosaP.aeruginosa isolated from Shanghai hospitals(%)isolated from Shanghai hospitals(%)Antimicrobial agentsAntimicrobial agents1993*1993*(232)(232)20002000(1790(1790)20012001(2302(2302)20022002(2457)(2457)20032003(2123)(2123)20042004(2287(2287)20052005(2520(2520)PiperacillinPiperacillin2424313133333030333333333434CeftazidimeCeftazidime8 8171721212020202024241919Cefoperazone Cefoperazone 2020262630302929303031312828CefepimeCefepime-17171616171717171515Piperacillin-tazobactamPiperacillin-tazobactam-29292727262626262424Ticarcillin-clavulanic acidTicarcillin-clavulanic acid-373747474747373743433838Cefoperazone-sulbactamCefoperazone-sulbactam-151515151414151515151313Imipenem Imipenem 6 6171724242626252521212121Meropenem Meropenem-14142121-171724242323Gentamicin Gentamicin 3636333334343535383833333232Amikacin Amikacin 8 8202023232121202020201717Ciprofloxacin Ciprofloxacin 1313282827271919252521212424*Testing year,number of isolates in the parenthesesMechanisms of resistance to imipenem in P.aeruginosan nProducing of Producing of-lactamases:-lactamases:carbapenemases carbapenemasesn nIMP,VIM,OXA,KPC,GIM,SPM familiesIMP,VIM,OXA,KPC,GIM,SPM families ESBLsESBLs AmpCAmpCnDecreased permeability:lost of porin D2n nActive effluxActive effluxXEffluxInactivationDecreasedpermeabilityTrends in antimicrobial resistance rates among strains of Trends in antimicrobial resistance rates among strains of Acinetobacter spp.Acinetobacter spp.isolated from Shanghai hospitals(%)isolated from Shanghai hospitals(%)Antimicrobial agentsAntimicrobial agents1999*1999*(1199)(1199)20002000(1365(1365)20012001(1851(1851)20022002(2056(2056)20032003(1686)(1686)20042004(2191)(2191)20052005(2418)(2418)PiperacillinPiperacillin4141515144444242494952525757CeftazidimeCeftazidime4040464630303838434345455050Cefoperazone Cefoperazone 6464-5757595965657979-CefepimeCefepime-333329292929353537374343Piperacillin-tazobactamPiperacillin-tazobactam1919-20202727303032323737Ampicillin-sulbactamAmpicillin-sulbactam1111161619192121191922223030Cefoperazone-sulbactamCefoperazone-sulbactam-5 56 68 89 91414Imipenem Imipenem 4 43 33 32 24 44 41010Meropenem Meropenem-4 43 3-5 56 61111Gentamicin Gentamicin 4242494942424141464650505454Amikacin Amikacin 3131333331313131333336364141Ciprofloxacin Ciprofloxacin 3737454537373838424246465050*Testing year,number of isolates in the parenthesesAntimicrobial resistance rates among ICU strains of Antimicrobial resistance rates among ICU strains of AcinetobacterAcinetobacter spp.in China between 2003 and spp.in China between 2003 and 2004(%)2004(%)(Wang H,et al.Chin J Lab Med 2005;28:1295)Antimicrobial agentsAntimicrobial agents2003200320042004CeftazidimeCeftazidime47475050CefepimeCefepime51515252Piperacillin-tazobactamPiperacillin-tazobactam27273030Cefoperazone-sulbactamCefoperazone-sulbactam11111313Imipenem Imipenem 4.54.51818MeropenemMeropenem4.54.51717Amikacin Amikacin 41415252Ciprofloxacin Ciprofloxacin 53535959Outbreak of carbapenem-resistant A.baumannii in Beijing and Guangzhou(Wang H,et al.Chin J Lab Med 2005;28:636)(Wang H,et al.Chin J Lab Med 2005;28:636)n nMDR-AB,resistant to 3 of the MDR-AB,resistant to 3 of the following 5 drugs:Pip/TAZ,following 5 drugs:Pip/TAZ,CAZ,Sul/CFP,Gen,Cip,ImiCAZ,Sul/CFP,Gen,Cip,Imi 5%in 1995 5%in 1995 67%in 2002 in 67%in 2002 in BJBJ 20%in 1998 20%in 1998 57%in 2002 57%in 2002 in GZin GZn n90%(35/39)strains produced 90%(35/39)strains produced OXA-23OXA-23 carbapenemase carbapenemasen nPFGE results indicated PFGE results indicated resistance colonies spread in resistance colonies spread in each of 4 hospitals,mainly in each of 4 hospitals,mainly in patients with VAP and surgical patients with VAP and surgical infectionsinfectionsLane 1-3,5,8,11-16 PFGE type A,indicating same colonyOutbreak of COS-AB in Shanghai(Yang L,et al.Natl Med J China 2006;86:592)(Yang L,et al.Natl Med J China 2006;86:592)n nOutbreak of COS-Outbreak of COS-AB(colistin-only-AB(colistin-only-sensitive sensitive A.A.baumanniibaumannii)in)in some hospitalssome hospitals PFGE type B strains PFGE type B strains caused outbreak of caused outbreak of COS-AB in burn ward in COS-AB in burn ward in a Shanghai hospitala Shanghai hospital PFGE type A strains of PFGE type A strains of COS-AB spread in COS-AB spread in surgical wardssurgical wards Lane 5-10,13-14,PFGE type A Lane 3-4,12,PFGE type BTrends in antimicrobial resistance rates among strains Trends in antimicrobial resistance rates among strains of of S.maltophiliaS.maltophilia isolated from Shanghai hospitals(%)isolated from Shanghai hospitals(%)Antimicrobial agentsAntimicrobial agents1999*1999*(271)(271)20002000(323)(323)20012001(581)(581)20022002(573)(573)20032003(448)(448)20042004(583)(583)20052005(751)(751)PiperacillinPiperacillin6969777759596565686874747373CeftazidimeCeftazidime5353373733334040383838383737Cefoperazone Cefoperazone 3838272722223333333344444242CefepimeCefepime-36364949383846464848Piperacillin-tazobactamPiperacillin-tazobactam-40405151565657575353Ticarcillin-clavulanic acidTicarcillin-clavulanic acid3636232313133333262630303535Cefoperazone-sulbactamCefoperazone-sulbactam-14149 91818171718182222Imipenem Imipenem 9191969696969898989898989797Meropenem Meropenem-898965655050797985858383Gentamicin Gen