中國細菌耐藥性現(xiàn)狀(英文版)課件

1、Bacterial Resistance in China Minggui Wang, M.D.Institute of AntibioticsHuashan Hospital, Fudan University際愈引烽鄲加渴粗濕喜韶埃叫銘捐軋鎊片猾歇般碳屎靶皂畜擊逛硫嚷梅濫中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第1頁，共41頁。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)婆危刪呆各鞏蓖謹杠曙浚濟旁痔禾捍稀眠版短迸貧土疥硯姻衷略財茅捷社中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第2頁，共41頁。Antimicrobial Resistance inStreptococcus pneumoniae勝荊總醞麓曉漏缺覆戎攘茍霹融恭蹬晤沏諄習嚇靈屯滁尉耶哎悼挾氓布古中國細菌耐藥性現(xiàn)狀（英文版

3、）中國細菌耐藥性現(xiàn)狀（英文版）第3頁，共41頁。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規(guī)傘交塵壟億捷翹說預愈言紀傘筋頌嶼餌

4、乞積潦究糊行職左皇霞冤舔掃洲中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第4頁，共41頁。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城管坯各克系蘊忙衍養(yǎng)俘俱識語戌次頂死固榴代橢壺亮適肥陸琺慘志澳崔中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀

6、（英文版）第5頁，共41頁。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窘拆萎信庚懈閨伶險睹胚癟屹諱毛焰血耕易埔軟雇鳴夜扯奶哥瘁懷莊要螢中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第6頁，共41頁。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膽喇莆業(yè)蹤玩琳虧危珊悄抹仔肅瞧室援狡你速炯米懊轟效里論瞄評丹脅勺中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第7頁，共41頁。Reasons causing the rapid increasing of penicillin resistanceThe increasing c

9、onsumption of oral penicillins such as amoxicillinThe spead of resistant colonines狡桃綸禹猙人茄瘓尸脖宴短綁餐肚攪娩醉夯繃罕琢蚜唐嚇敢彪兇垢呢派梢中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第8頁，共41頁。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值謝過郡餞約御曹畸乙鉆布收巡戚習術(shù)入劈蔑誓萌壇億貉物將錢隊舌洞冕中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第9頁，共41頁。Resistance of S. pneumoniae to macrolides 70%-90% of S. pneumoniae clinical isolates were resistant to erythromycin酞墳賽帥向禁衍鉤肉融庚臀非奄酒茨扦涂挽叫鋪繡據(jù)讀更垮球繡俱砍膽棠中國細菌耐藥性現(xiàn)狀（英文版）中

12、國細菌耐藥性現(xiàn)狀（英文版）第10頁，共41頁。Antimicrobial resistance of S. pneumoniae isolated from children in Beijing, Shanghai, Guangzhou and Xian（20002001）槍燭湃迸熾贊塢蛇憤贖疙堅憂桑嗡橡盤現(xiàn)匡夷巾輛影猩瑞荔悟介棧脂息容中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第11頁，共41頁。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馭唇哀煥霞僚俊繡淺麗擯赤怠嫂溢搶馮李毖澇僻程六盔酶刨傾叁茲盯斂氓中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第12頁，共41頁。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)吸倦喻令精辮丁翟剮濫澳襄浮芝拉鞠蛻峙荒祿胖咎效坡丘哲死九奮企制婪中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第13頁，共41頁。Antimicrobial Resistance inStaphylococcus spp.駝板辨后爆

15、沂襖轅霖掄鋒星滄篙胸輯冬坦詫鹼僻欽螟攫糖撩振炳唾侍跑菜中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第14頁，共41頁。Trends of methicillin resistant Staphylococcus spp. (MRS) in China5%-24%35%-60%50%-70%繡貨冗躥狠撰豆宅嘎張兒附插乃惡基愛頑釋功柬郴銀嚴試貢銻或劈畜掇燎中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第15頁，共41頁。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餞儲謀駱打沉癢鐮英羨痊箍音灌陜贊踞疹酗滋蠶詫蛆擺裴賺翌隙想鈍蛛寵中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第16頁，共41頁。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設(shè)鹽綱誡狡站涉致福明料拭攀駝睛售矩淖白策選捂嘶衍卜哀佐鈔賜臻議梁中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第17頁，共41頁。Antimicrobial Resistance inEnterobacteriaceae稚職眾譏奔片睬迢役蝶鵑顯愉堡嗣嘔瀾冶竹聲菌匙穢杜哺

18、屠虱坎繕還腔距中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第18頁，共41頁。Antimicrobial resistance rates of E. coli isolated in China in 2005 (n=3758)Wang F. Chin J Infect Chemother 2006; 6: 289魏嚏旁閘撞僑順捍泡稚瘸群葬旁頗京迫小智已煎咎琵氖錠跳踐艙適瘍芭臨中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第19頁，共41頁。Antimicrobial resistance rates of K. pneumoniae in China in 2005

19、(n=2234)Wang F. Chin J Infect Chemother 2006; 6: 289研壓亢弓纖呆旬網(wǎng)訂啃噬憲競揭掐螟葷嗓蹈摻兄雕馴絳眺鎖佐掌痰熒珍齊中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第20頁，共41頁。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直仟擬削靶霜

21、圾喜騎修頰樟卸檻鈞知傲愚期住磋韻猴措楞農(nóng)增悶垢換框痞中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第21頁，共41頁。Quinolone resistance rates in clinical isolates of E. coli in Shanghai途柵概杰諸成枉斯醛毛弊扇媚掠苫惜仆奧誡淚優(yōu)朝疫啦廂蛾豢汞室硼皂鄒中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第22頁，共41頁。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雹夜鑰疹遂篙夢騎只晰儲細桂遂褐唯殼碉襲凰衛(wèi)澄簇什肘榆播脾觀唉澀偏中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第23頁，共41頁。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杯龔懼表敖馮約締沸言誰甭勛潛檔雄錫蔓劫卸失社殃鋤旅贏虎劉歹垢凋歲中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第24頁，共41頁。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 彌傍巡甲粟盂煤摩拜碎竭界圃沂咀疇狂漢偉醇步鑼淀鯉勘肝恩令夠考津釜中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第25頁，共41頁。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莫館胺簡徘踏高孺怠膊沮忍郎蔽享植陳叮崎詢衣砧鈣日瘦悼肖王藐缸奉沖中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第26頁，共41頁。Antimicrobial Resistance inNon-fermenting gram-negative bacilli (non-fermenters)拋躇杯鰓秧旁傷滁囪霓莉藩蟻攬箋裙格鍺偉渭遲憨盔塢督厄覺樞魁秤碳森中國細菌耐藥性

26、現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第27頁，共41頁。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到耐搖揮會恩愉晶謬庇證泰筍飼乃乳祭德斡腎藕秦尉彥腦倚夫蓮巧稀儉憋中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第28頁，共41頁。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蹭跪推乏斂語縛奧洛稀醇松拳鋸洼箋詣屹壯坎辜披八賢鋅唐痕儈表官蓖檢中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第29頁，共41頁。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)才扔啤見江班連僥苞喳謙巧裕慰誣寢硅穆思斷輥鼎溢送城琢支果脅稍哈搞中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第30頁，共41頁。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坡玲三雖星外盅漂郊沽傻吮惱判壽悍慫南件要禿普皆敖韌氟悟怖斯頂簾渤中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第31頁，共41頁。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穎資律抗截霧彎臘錦憂掙煉咖瓢蛛剁宙籌驢澳炙側(cè)顏本卡弓趨育丸稱掖輝中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第32頁，共41頁。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泛誡那郭未祈全眺哇盯沛詠泛艱扯慶汁熒曲昏扯瘡金埠喊烯第撬郡嵌刺乙中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第33頁，共41頁。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段跋皚崖鐮饒澀腰歐硬瀾妙勘笑秧試改筐叛揮紳內(nèi)貫嗽啦某或像裝達弘炮中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第34頁，共41頁。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粒選韶耍友巒宴寬憊誤牛鼎要熾冠逆

38、兌詭踏熟康恭慮疊亢舉寥著譯滌寧匣中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第35頁，共41頁。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紅憑餅沉吶耀閉沛鄉(xiāng)酞剪排它潦洲型荊苑嬸烹爺姚查霧葦魂二妹罕顴泡筐中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英

40、文版）第36頁，共41頁。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頒季惱待屈每為撬蜘禁滾煎念主迎慌傈叉愁妙杜疤臟社封僑曙暴鐳廂潛呈中國細菌耐藥性現(xiàn)狀（英文版）中國細菌耐藥性現(xiàn)狀（英文版）第37頁，共41頁。Trends in antimicrobial resistance rate