中國(guó)細(xì)菌耐藥性現(xiàn)狀（英文版）課件

1、Bacterial Resistance in China Minggui Wang, M.D.Institute of AntibioticsHuashan Hospital, Fudan UniversityOutlineAntimicrobial Resistance and Its MechanismsGram-positive cocciStreptococcus pneumoniaeStaphylococcus spp.Gram-negative bacilliEnterobacteriaceaeEscherichia coliKlebsiella spp.Enterobacter

2、 spp., et al.Non-fermenting gram-negative bacilli (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 PRSPRe

3、gional problemGlobal problem-lactams (penicillin)MacrolidesFluoroquinolonesPenicillin resistance in S. pneumoniae in China in late 1990YearRegionPopulationSourceNo. of StrainsPNSSP(%)PISP(%)PRSP(%)96-99ShanghaiAdultsClinical68330ChildrenClinical60131301998ChildrenCarriage222141401998GuangzhouClinica

4、l10212120ChildrenCarriage151151501997*BejingClinical7914112ChildrenCarriage 2441413199-004 centers Clinical55314122PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae* AAC 1998; 42: 2633Penicillin resistance in S. pne

5、umoniae in China in early 2000YearRegionPopulationSourceNo. of StrainsPNSSP(%)PISP(%)PRSP(%)2001ShanghaiChildrenClinical 1005549601-02BeijingShenyangClinical19243321100-023 centersChildrenClinical8874034600-014 centersChildrenClinical 62441374PNSSP, penicillin non-susceptible S. pneumoniae; PISP, pe

6、nicillin 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

7、strains isolated from Childrens HospitalResistance of S. pneumoniae to macrolides 70%-90% of S. pneumoniae clinical isolates were resistant to erythromycinAntimicrobial resistance of S. pneumoniae isolated from children in Beijing, Shanghai, Guangzhou and Xian（20002001）Mechanism of bacterial resista

8、nce:Mosaic PBP Genes in PRSPPenicillin resistance is due to alterations in endogenous PBPsDNA from related streptococci taken up and incorporated into S. pneumoniae genesCzechoslovakia (1987)USA (1983)South Africa (1978)S SXN pen-sensitive S. pneumoniaeStreptococcus ?PBP 2bMechanism of MRSAMRSA cont

9、ain novel PBP2a, substitutes for native PBPs; low affinity for all -lactamsPBP2a is encoded by mecA gene; expression controlled by mecI, mecR1 and other factorsSummaryAntimicrobial resistance in gram-positive cocciPenicillin resistance in S. pneumoniae has been increasing markedly since 2000 in Chin

10、aThe resistance rates of S. pneumoniae to macrolides such as erythromycin are very highMethicillin-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

11、; 6: 289Extended-spectrum -lactamases (ESBLs) in Enterobacteriaceae in ChinaESBL-producing strains Hospital-acquired infections1:E. coli, 11-47%K. pneumoniae, 14-51%Community-acquired infections2:E. coli, 16%K. pneumoniae, 17%The main genotype of ESBLs is CTX-M1, typically provides resistance to cef

12、taxime but often not to ceftazidime or aztreonam31, 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 resistanceAlterat

13、ions in drug target enzymes (DNA gyrase and/or topoisomerase IV) Alterations in drug accumulation (active efflux system) Both result from chromosomal mutations Target modificationEffluxPlasmid-mediated quinolone resistance: qnr determinatsRSRRSRConjugationTransformationRqnrqnrA: Lancet, 1998, the U.

14、S.qnrB: AAC, 2006, the U. S.qnrS: AAC, 2005, JapanqnrC: 7th NCCM, 2007, ChinaPlasmid-mediated quinolone resistanceqnr family: qnrA, qnrB, qnrS, qnrC Protection of quinolone targetsaac(6)-Ib-cr (2006) aminoglycoside acetyltransferaseqepA (2007) quinolone efflux pump SummaryAntimicrobial resistance in

15、 gram-negative bacilliESBLs-producing strains of E. coli and K. pneumoniae are common, and spreading from hospital to communityQuinolone resistance rates in E. coli are especially highNew mechanisms of plasmid-mediated quinolone resistance emergedAntimicrobial Resistance inNon-fermenting gram-negati

16、ve bacilli (non-fermenters)Importance of non-fermenters Non-fermenting gram-negative bacilli (non-fermenters) include:Pseudomonas aeruginosaAcinetobacter spp.Stenotrophomonas maltophiliaAlcaligenes spp.Burkholderia sppFlavobacterium (Chryseobaterium) spp. , et alNon-fermenters are highly resistant t

17、o commonly used antimicrobialsThe infections of non-fermenters are difficult to 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)146016321215117113691661202830283275300552425656481858195665YearNo

18、 of strainsHigh incidence of non-fermenters in Gram-negative bacilli45% (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)Non-fermenters increased from 41% in 1999 to 48% in

19、 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 against 8 antimicrobials in CHINET in 2005 (Wang F. Chin J Infect Chemother 2006; 6

20、:289 )Antimicrobial agentsResistance rate (%)Susceptibility rate (%)Ceftazidime4152Cefepime4546Piperacillin-tazobactam4449Cefoperazone-sulbactam2352Imipenem 4354Meropenem4355Ciprofloxacin4148Amikacin4648Trends in antimicrobial resistance rates among strains of P. aeruginosa isolated from Shanghai ho

21、spitals(%)Antimicrobial agents1993*(232)2000(1790)2001(2302)2002(2457)2003(2123)2004(2287)2005(2520)Piperacillin24313330333334Ceftazidime8172120202419Cefoperazone 20263029303128Cefepime-1716171715Piperacillin-tazobactam-2927262624Ticarcillin-clavulanic acid-374747374338Cefoperazone-sulbactam-1515141

22、51513Imipenem 6172426252121Meropenem -1421-172423Gentamicin 36333435383332Amikacin 8202321202017Ciprofloxacin 13282719252124* Testing year, number of isolates in the parenthesesMechanisms of resistance to imipenem in P. aeruginosaProducing of -lactamases: carbapenemasesIMP, VIM, OXA, KPC, GIM, SPM f

23、amiliesESBLsAmpCDecreased permeability: lost of porin D2Active effluxXEffluxInactivationDecreasedpermeabilityTrends in antimicrobial resistance rates among strains of Acinetobacter spp. isolated from Shanghai hospitals(%)Antimicrobial agents1999*(1199)2000(1365)2001(1851)2002(2056)2003(1686)2004(219

24、1)2005(2418)Piperacillin41514442495257Ceftazidime40463038434550Cefoperazone 64-57596579-Cefepime-332929353743Piperacillin-tazobactam19-2027303237Ampicillin-sulbactam11161921192230Cefoperazone-sulbactam-568914Imipenem 43324410Meropenem -43-5611Gentamicin 42494241465054Amikacin 31333131333641Ciproflox

25、acin 37453738424650* Testing year, number of isolates in the parenthesesAntimicrobial resistance rates among ICU strains of Acinetobacter spp. in China between 2003 and 2004(%) (Wang H, et al. Chin J Lab Med 2005; 28: 1295)Antimicrobial agents20032004Ceftazidime4750Cefepime5152Piperacillin-tazobacta

26、m2730Cefoperazone-sulbactam1113Imipenem 4.518Meropenem4.517Amikacin 4152Ciprofloxacin 5359Outbreak of carbapenem-resistant A. baumannii in Beijing and Guangzhou(Wang H, et al. Chin J Lab Med 2005; 28: 636)MDR-AB, resistant to 3 of the following 5 drugs: Pip/TAZ, CAZ, Sul/CFP, Gen, Cip, Imi 5% in 199

27、5 67% in 2002 in BJ 20% in 1998 57% in 2002 in GZ90%(35/39) strains produced OXA-23 carbapenemasePFGE results indicated resistance colonies spread in each of 4 hospitals, mainly in patients with VAP and surgical infectionsLane 1-3, 5, 8, 11-16 PFGE type A, indicating same colonyOutbreak of COS-AB in

28、 Shanghai(Yang L, et al. Natl Med J China 2006; 86: 592)Outbreak of COS-AB (colistin-only-sensitive A. baumannii) in some hospitalsPFGE type B strains caused outbreak of COS-AB in burn ward in a Shanghai hospitalPFGE type A strains of COS-AB spread in surgical wards Lane 5-10, 13-14, PFGE type A Lane 3-4, 12, PFGE type BTrends in antimicrobial resistance rates among strains of S. maltophilia isolated from Shanghai hospitals(%)Antimicrobial agents1999*(271)2000(323)2001(581)2