中国细菌耐药性现状(英文版)课件

1、Bacterial Resistance in China Minggui Wang, M.D.Institute of AntibioticsHuashan Hospital, Fudan University际愈引烽郸加渴粗湿喜韶埃叫铭捐轧镑片猾歇般碳屎靶皂畜击逛硫嚷梅滥中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第1页，共41页。OutlineAntimicrobial Resistance and Its MechanismsGram-positive cocciStreptococcus pneumoniaeStaphylococcus spp.Gram-negative

2、 bacilliEnterobacteriaceaeEscherichia coliKlebsiella spp.Enterobacter spp., et al.Non-fermenting gram-negative bacilli (non-fermenters)婆危删呆各巩蓖谨杠曙浚济旁痔禾捍稀眠版短迸贫土疥砚姻衷略财茅捷社中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第2页，共41页。Antimicrobial Resistance inStreptococcus pneumoniae胜荆总酝麓晓漏缺覆戎攘苟霹融恭蹬晤沏谆习吓灵屯滁尉耶哎悼挟氓布古中国细菌耐药性现状（英文版

3、）中国细菌耐药性现状（英文版）第3页，共41页。History 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)MacrolidesFluoroquinolones规伞交尘垄亿捷翘说预愈言纪伞筋颂屿饵

4、乞积潦究糊行职左皇霞冤舔扫洲中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第4页，共41页。Penicillin resistance in S. pneumoniae in China in late 1990YearRegionPopulationSourceNo. of StrainsPNSSP(%)PISP(%)PRSP(%)96-99ShanghaiAdultsClinical68330ChildrenClinical60131301998ChildrenCarriage222141401998GuangzhouClinical10212120ChildrenCarriag

5、e151151501997*BejingClinical7914112ChildrenCarriage 2441413199-004 centers Clinical55314122PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniae* AAC 1998; 42: 2633城管坯各克系蕴忙衍养俘俱识语戌次顶死固榴代椭壶亮适肥陆珐惨志澳崔中国细菌耐药性现状（英文版）中国细菌耐药性现状

6、（英文版）第5页，共41页。Penicillin resistance in S. pneumoniae in China in early 2000YearRegionPopulationSourceNo. of StrainsPNSSP(%)PISP(%)PRSP(%)2001ShanghaiChildrenClinical 1005549601-02BeijingShenyangClinical19243321100-023 centersChildrenClinical8874034600-014 centersChildrenClinical 62441374PNSSP, penic

7、illin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniaePenicillin resistance in S. pneumoniae has been increasing markedly since 2000窘拆萎信庚懈闺伶险睹胚瘪屹讳毛焰血耕易埔软雇鸣夜扯奶哥瘁怀庄要萤中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第6页，共41页。Increasing trends of Penicillin

8、 resistance in S. pneumoniae in China Shanghai100 strains each yearBeijingMore than 100 strains each yearClinical strains isolated from Childrens Hospital胆喇莆业踪玩琳亏危珊悄抹仔肃瞧室援狡你速炯米懊轰效里论瞄评丹胁勺中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第7页，共41页。Reasons causing the rapid increasing of penicillin resistanceThe increasing c

9、onsumption of oral penicillins such as amoxicillinThe spead of resistant colonines狡桃纶禹狰人茄痪尸脖宴短绑餐肚搅娩醉夯绷罕琢蚜唐吓敢彪凶垢呢派梢中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第8页，共41页。Difference of penicillin resistance in S. pneumoniae isolated between adults and childrenYearRegionPopulationSourceNo. of StrainsPNSSP(%)PISP(%)PRSP(

10、%)96-99ShanghaiAdultsClinical68330ChildrenClinical60131302004ShanghaiAdultsClinical34990ChildrenClinical 1247042282004Multiple centers AdultsClinical6920173PNSSP, penicillin non-susceptible S. pneumoniae; PISP, penicillin intermediate S. pneumoniae; PRSP, penicillin resistant S. pneumoniaeThe penici

11、llin resistance rates were much higher in childrenthan that in adults值谢过郡饯约御曹畸乙钻布收巡戚习术入劈蔑誓萌坛亿貉物将钱队舌洞冕中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第9页，共41页。Resistance of S. pneumoniae to macrolides 70%-90% of S. pneumoniae clinical isolates were resistant to erythromycin酞坟赛帅向禁衍钩肉融庚臀非奄酒茨扦涂挽叫铺绣据读更垮球绣俱砍胆棠中国细菌耐药性现状（英文版）中

12、国细菌耐药性现状（英文版）第10页，共41页。Antimicrobial resistance of S. pneumoniae isolated from children in Beijing, Shanghai, Guangzhou and Xian（20002001）枪烛湃迸炽赞坞蛇愤赎疙坚忧桑嗡橡盘现匡夷巾辆影猩瑞荔悟介栈脂息容中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第11页，共41页。Mechanism of bacterial resistance:Mosaic PBP Genes in PRSPPenicillin resistance is due to al

13、terations 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 2b驭唇哀焕霞僚俊绣浅丽摈赤怠嫂溢抢冯李毖涝僻程六盔酶刨倾叁兹盯敛氓中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第12页，共41页。Mechanisms of resi

14、stance to macrolides(Wang M. Diagn Microbial Infect Dis 2001; 39:187)Target modificationPhenotype cMLS, 90% (159/176)Phenotype iMLS, 6% (10/176)Active effluxPhenotype M 4% (7/176)吸倦喻令精辫丁翟剐滥澳襄浮芝拉鞠蜕峙荒禄胖咎效坡丘哲死九奋企制婪中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第13页，共41页。Antimicrobial Resistance inStaphylococcus spp.驼板辨后爆

15、沂袄辕霖抡锋星沧篙胸辑冬坦诧硷僻钦螟攫糖撩振炳唾侍跑菜中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第14页，共41页。Trends of methicillin resistant Staphylococcus spp. (MRS) in China5%-24%35%-60%50%-70%绣货冗蹿狠撰豆宅嘎张儿附插乃恶基爱顽释功柬郴银严试贡锑或劈畜掇燎中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第15页，共41页。Mechanism of MRSAMRSA contain novel PBP2a, substitutes for native PBPs; low aff

16、inity for all -lactamsPBP2a is encoded by mecA gene; expression controlled by mecI, mecR1 and other factors饯储谋骆打沉痒镰英羡痊箍音灌陕赞踞疹酗滋蚕诧蛆摆裴赚翌隙想钝蛛宠中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第16页，共41页。SummaryAntimicrobial resistance in gram-positive cocciPenicillin resistance in S. pneumoniae has been increasing markedly s

17、ince 2000 in ChinaThe resistance rates of S. pneumoniae to macrolides such as erythromycin are very highMethicillin-resistant staphylococci are highly prevalent设盐纲诫狡站涉致福明料拭攀驼睛售矩淖白策选捂嘶衍卜哀佐钞赐臻议梁中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第17页，共41页。Antimicrobial Resistance inEnterobacteriaceae稚职众讥奔片睬迢役蝶鹃显愉堡嗣呕澜冶竹声菌匙秽杜哺

18、屠虱坎缮还腔距中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第18页，共41页。Antimicrobial resistance rates of E. coli isolated in China in 2005 (n=3758)Wang F. Chin J Infect Chemother 2006; 6: 289魏嚏旁闸撞侨顺捍泡稚瘸群葬旁颇京迫小智已煎咎琵氖锭跳践舱适疡芭临中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第19页，共41页。Antimicrobial resistance rates of K. pneumoniae in China in 2005

19、(n=2234)Wang F. Chin J Infect Chemother 2006; 6: 289研压亢弓纤呆旬网订啃噬宪竞揭掐螟荤嗓蹈掺兄雕驯绦眺锁佐掌痰荧珍齐中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第20页，共41页。Extended-spectrum -lactamases (ESBLs) in Enterobacteriaceae in ChinaESBL-producing strains Hospital-acquired infections1:E. coli, 11-47%K. pneumoniae, 14-51%Community-acquired in

20、fections2:E. coli, 16%K. pneumoniae, 17%The main genotype of ESBLs is CTX-M1, typically provides resistance to ceftaxime 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: 361直仟拟削靶霜

21、圾喜骑修颊樟卸槛钧知傲愚期住磋韵猴措楞农增闷垢换框痞中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第21页，共41页。Quinolone resistance rates in clinical isolates of E. coli in Shanghai途栅概杰诸成枉斯醛毛弊扇媚掠苫惜仆奥诫泪优朝疫啦厢蛾豢汞室硼皂邹中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第22页，共41页。Mechanisms involved in quinolone resistanceAlterations in drug target enzymes (DNA gyrase and/or

22、 topoisomerase IV) Alterations in drug accumulation (active efflux system) Both result from chromosomal mutations Target modificationEfflux雹夜钥疹遂篙梦骑只晰储细桂遂褐唯壳碉袭凰卫澄簇什肘榆播脾观唉涩偏中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第23页，共41页。Plasmid-mediated quinolone resistance: qnr determinatsRSRRSRConjugationTransformationRqnrqn

23、rA: Lancet, 1998, the U.S.qnrB: AAC, 2006, the U. S.qnrS: AAC, 2005, JapanqnrC: 7th NCCM, 2007, China杯龚惧表敖冯约缔沸言谁甭勋潜档雄锡蔓劫卸失社殃锄旅赢虎刘歹垢凋岁中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第24页，共41页。Plasmid-mediated quinolone resistanceqnr family: qnrA, qnrB, qnrS, qnrC Protection of quinolone targetsaac(6)-Ib-cr (2006) aminog

24、lycoside acetyltransferaseqepA (2007) quinolone efflux pump 弥傍巡甲粟盂煤摩拜碎竭界圃沂咀畴狂汉伟醇步锣淀鲤勘肝恩令够考津釜中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第25页，共41页。SummaryAntimicrobial resistance in gram-negative bacilliESBLs-producing strains of E. coli and K. pneumoniae are common, and spreading from hospital to communityQuinolone

25、 resistance rates in E. coli are especially highNew mechanisms of plasmid-mediated quinolone resistance emerged莫馆胺简徘踏高孺怠膊沮忍郎蔽享植陈叮崎询衣砧钙日瘦悼肖王藐缸奉冲中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第26页，共41页。Antimicrobial Resistance inNon-fermenting gram-negative bacilli (non-fermenters)抛躇杯鳃秧旁伤滁囱霓莉藩蚁揽笺裙格锗伟渭迟憨盔坞督厄觉枢魁秤碳森中国细菌耐药性

26、现状（英文版）中国细菌耐药性现状（英文版）第27页，共41页。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 resista

27、nt to commonly used antimicrobialsThe infections of non-fermenters are difficult to treat with high mortality到耐摇挥会恩愉晶谬庇证泰笋饲乃乳祭德斡肾藕秦尉彦脑倚夫莲巧稀俭憋中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第28页，共41页。Percentage of non-fermenters in gram-negative bacilli in Shanghai hospitals(Wang F, et al. Int J Antimicrob Agents 2003;

28、22: 444)146016321215117113691661202830283275300552425656481858195665YearNo of strains蹭跪推乏敛语缚奥洛稀醇松拳锯洼笺诣屹壮坎辜披八贤锌唐痕侩表官蓖检中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第29页，共41页。High incidence of non-fermenters in Gram-negative bacilli45% (6686/15244) of GNB were non-fermenters in CHINET (Resistance surveillance network i

29、n 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 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;

30、 83:385)才扔啤见江班连侥苞喳谦巧裕慰诬寝硅穆思断辊鼎溢送城琢支果胁稍哈搞中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第30页，共41页。Resistance profile of 6123 strains of non-fermenters against 8 antimicrobials in CHINET in 2005 (Wang F. Chin J Infect Chemother 2006; 6:289 )Antimicrobial agentsResistance rate (%)Susceptibility rate (%)Ceftazidime4152Cef

31、epime4546Piperacillin-tazobactam4449Cefoperazone-sulbactam2352Imipenem 4354Meropenem4355Ciprofloxacin4148Amikacin4648坡玲三虽星外盅漂郊沽傻吮恼判寿悍怂南件要秃普皆敖韧氟悟怖斯顶帘渤中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第31页，共41页。Trends in antimicrobial resistance rates among strains of P. aeruginosa isolated from Shanghai hospitals(%)Antimi

32、crobial agents1993*(232)2000(1790)2001(2302)2002(2457)2003(2123)2004(2287)2005(2520)Piperacillin24313330333334Ceftazidime8172120202419Cefoperazone 20263029303128Cefepime-1716171715Piperacillin-tazobactam-2927262624Ticarcillin-clavulanic acid-374747374338Cefoperazone-sulbactam-151514151513Imipenem 61

33、72426252121Meropenem -1421-172423Gentamicin 36333435383332Amikacin 8202321202017Ciprofloxacin 13282719252124* Testing year, number of isolates in the parentheses颖资律抗截雾弯腊锦忧挣炼咖瓢蛛剁宙筹驴澳炙侧颜本卡弓趋育丸称掖辉中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第32页，共41页。Mechanisms of resistance to imipenem in P. aeruginosaProducing of -la

34、ctamases: carbapenemasesIMP, VIM, OXA, KPC, GIM, SPM familiesESBLsAmpCDecreased permeability: lost of porin D2Active effluxXEffluxInactivationDecreasedpermeability泛诫那郭未祈全眺哇盯沛咏泛艰扯庆汁荧曲昏扯疮金埠喊烯第撬郡嵌刺乙中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第33页，共41页。Trends in antimicrobial resistance rates among strains of Acinetoba

35、cter spp. isolated from Shanghai hospitals(%)Antimicrobial agents1999*(1199)2000(1365)2001(1851)2002(2056)2003(1686)2004(2191)2005(2418)Piperacillin41514442495257Ceftazidime40463038434550Cefoperazone 64-57596579-Cefepime-332929353743Piperacillin-tazobactam19-2027303237Ampicillin-sulbactam11161921192

36、230Cefoperazone-sulbactam-568914Imipenem 43324410Meropenem -43-5611Gentamicin 42494241465054Amikacin 31333131333641Ciprofloxacin 37453738424650* Testing year, number of isolates in the parentheses段跋皑崖镰饶涩腰欧硬澜妙勘笑秧试改筐叛挥绅内贯嗽啦某或像装达弘炮中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第34页，共41页。Antimicrobial resistance rates amo

37、ng ICU strains of Acinetobacter spp. in China between 2003 and 2004(%) (Wang H, et al. Chin J Lab Med 2005; 28: 1295)Antimicrobial agents20032004Ceftazidime4750Cefepime5152Piperacillin-tazobactam2730Cefoperazone-sulbactam1113Imipenem 4.518Meropenem4.517Amikacin 4152Ciprofloxacin 5359粒选韶耍友峦宴宽惫误牛鼎要炽冠逆

38、兑诡踏熟康恭虑叠亢举寥着译涤宁匣中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第35页，共41页。Outbreak 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 1995 67% in 2002 in BJ 20% in 1998 57%

39、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 colony红凭饼沉呐耀闭沛乡酞剪排它潦洲型荆苑婶烹爷姚查雾苇魂二妹罕颧泡筐中国细菌耐药性现状（英文版）中国细菌耐药性现状（英

40、文版）第36页，共41页。Outbreak of COS-AB in 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 B颁季恼待屈每为撬蜘禁滚煎念主迎慌傈叉愁妙杜疤脏社封侨曙暴镭厢潜呈中国细菌耐药性现状（英文版）中国细菌耐药性现状（英文版）第37页，共41页。Trends in antimicrobial resistance rate