上海交通大学医学院 新华 儿童 儿童医学中心 儿科学 之 CA-MRSA-09.10

MRSA感染趋势和治疗进展上海市儿童医院上海交通大学附属儿童医院呼吸科陆敏上海市儿童医院ShanghaiChildren’sSTAPHYLOCOCCUSstaphyle-abunchofgrapeskokkus-berry金黄色葡萄球菌

StaphylococcusAureus1928所有葡萄球菌对青霉素敏感1942首次从病人分离耐青霉素的葡萄球菌1950‘s医院内耐青霉素葡萄球菌大流行头孢霉素、红霉素、万古霉素1960甲氧西林耐青霉素酶1961首次在伦敦出现MRSA金黄色葡萄球菌耐药Methicillin-resistantStaphylococcusaureus(MRSA)difficult-to-treatinfectionsmultidrug-resistantSAoroxacillin-resistantSA(ORSA)resistanttoalargegroupofantibioticscalledthebeta-lactamspenicillins

cephalosporins EuropeMRSA 28%VRE(E.faecium) 8(22)%SP/penicillin 15%Jones,RN.PersonalCommunications,February2008

UnitedStatesMRSA54%VRE(E.faecium)27(72)%SP/penicillin15%

AsiaPacificMRSA 42%VRE(E.faecium) 5(10)%SP/penicillin

32%

LatinAmericaMRSA 38%VRE(E.faecium) 9(36)%SP/penicillin 13%G+全球耐药状况（2005-2006)WangHetal.DiagnMicrobiolInfectDis2008;62:226-9.PrevalenceofMRSAinChina798isolates,2005,12Cities,ChinaCHINET2007,ChinaMRSA58%(1963/3384)MRSAMRSAinfectionsinhospitalsfrom127,000in1999to278,000in2005annualdeathsincreasedfrom11,000tomorethan17,000atthesametimeMRSAresponsiblefor94,360seriousinfectionsandassociatedwith18,650hospitalstay-relateddeathsintheUnitedStatesin2005EmergInfectDis.(2007).13(12):1840–6.JAMA,2007,Oct,298:1803MRSAdeaths>AIDSintheU.S.eachyear80年代初，首次报道从静脉吸毒者或经常接触护理机构的高危人群种分离出MRSA80年代后期，首次报道从经常接触护理所的儿童中分离到MRSA1990‘s中期，芝加哥大学报道住院病人MRSA增加25倍1999年报道4例儿童死于致死性社区获得性MRSA（CA-MRSA）感染，这些儿童并无MRSA易感因素CA-MRSA出现美国CDC将CA-MRSA定义：门诊或住院后48小时内分离到MRSA菌株一年内无养老院、护理院或医院住院史，无透析或手术史、无永久性经皮留置体内的导管或医疗装置，无MRSA感染史和定殖史的患者，CA-MRSA定义多中心监测显示：社区获得MRSA为12％美国郊区74％MRSA感染是社区获得的，提示在这一地区MRSA已取代了MSSAmata分析显示：总CA-MRSA发生率分别占住院MRSA病人的30.2％和37.3％1.3％的社区人群有MRSA定殖CA-MRSA2001-2002surveillanceinUS1647CA-MRSAinfection8-20%werenotassociatedwithtraditionalriskfactors-CA-MRSAMostwereassociatedwithclinicallyrelevantinfectionsthatrequiredtreatmentManypatientswerechildrenwhorequiredhospitalizationWashingtonPost.Retrievedon2007-10-19

Community-acquiredMRSAinAsiaANSORPSurveillanceinAsia-2005-6%部分亚洲国家MRSA发病率高于西方国家,占院内金黄色葡萄球菌标本的70％台湾北部儿童CA-MRSA占CA-SA感染的74％。新加坡CA-MRSA非常少见我国MRSA占SA的60％以上上海儿童CA-MRSA占MRSA17%，占SA1%CA-MRSACA-MRSA引起皮肤和软组织感染、肺炎、中耳炎、败血症和尿路感染传统使用头孢菌素治疗社区获得性皮肤和软组织感染可能会失败，导致致死性感染体外敏感试验显示：CA-MRSA通常耐β内酰胺类抗生素，但对其他抗生素敏感，而多数HA-MRSA对多种抗生素耐药致死性感染的CA-MRSA含有Panlon-Valentine基因（pvl）和肠毒素C和H基因（sec和seh）CA-MRSA特征CA-MRSA:WhatitdoesCA-MRSA：比MSSA引起更深、更侵袭性感染，尤其是坏死性肺炎CA-MRSA：比MSSA更多坏死性筋膜炎CA-MRSA：引起菌血症并不很多CA-MRSA：更多引起反复感染皮肤软组织感染SSTIs80%ofCA-MRSAinfectionsareSSTIs,Necroticskinlesionsarealsoacommonpresentationandareoftenincorrectlyattributedtobitesbybrownreclusespidersorotherinsects.Generally,CA-MRSASSTIsarenotlife-threateninginvasiveinfection(eg,bacteremia,necrotizingfasciitis)canbecomedifficulttotreatandevencausedeath.坏死性筋膜炎NecrotizingfasciitisUSA300,SCCmecIV危险因素:preMRSA,HepCvirusinfection,diabetes,currentorpastinjectiondruguse,cancer,andHIV皮肤软组织感染SSTIsCA-MRSA7天婴儿，激惹和迅速增多皮疹CA-MRSAMRSA坏死性筋膜炎MRSA坏死性筋膜炎蜂窝织炎（短箭）脂膜炎（长箭）筋膜炎（箭头）革兰氏阳性球菌植皮后2周MRSA坏死性筋膜炎常见于热带地区，温带地区也有增加，尤其HIVCA-MRSA可能成为化脓性肌炎常见的病原45previouslyhealthychildreninwhomepisodesofbacterialmyositisorpyomyositisoccurred,26ofthesechildren(57.8%)--SA15ofthesepatients(57.7%)--CA-MRSA化脓性肌炎Pyomyositis.MRSAOsteomyelitisNecrotizingpneumonia(CAP)Post–influenzavirusinfectionInfluenzalikeillness(Post–influenzapneumonia)15casesofMRSACAPfrom9states(CDC),2003-2004influenzaseason4deaths(fatalityrate,26.7%)10severeMRSACAP,6deaths(fatalityrate,60%)2006.12-2007.1MRSA肺炎MRSA肺炎后期MRSA肺炎后期脓毒症SepsisWithorwithoutWaterhouse-Friderichsensyndromein2005,3fatalcasesattributedtoSaureusinfectioninchildrenwerereported,2CA-MRSA14previouslyhealthychildrenpresentedwithseveresepsis,12hadCA-MRSAsepsisOthermanifestationsSuppurativelymphadenitis,ophthalmicinfections(preseptalcellulitis,lidabscess,conjunctivitis,cornealulcers）otitismedia,sinusitis,food-borneGIillness分子生物学特征SA对甲氧西林耐药是由于低亲和力青霉素结合蛋白（PBP2a或PBP2’）编码PBP2a的mecA基因位于其调节基因mecI和mecR以及ccr元件组成的葡萄球菌染色体盒(SCCmec)7种SCCmec（Ⅰ－Ⅶ）基因型。SCCmecⅠ、Ⅱ、Ⅲ型中mecA复合体下游带有多个质粒和转座子，携带多种耐药基因，可产生多重耐药SCCmecⅣ和SCCmecⅤ型基因盒中除mecA外不带任何其他耐药基因故仅对β内酰胺类抗生素耐药，多见于CA-MRSA所有MRSA含SCCmec携带的mecA基因mecA基因编码78kDa低亲和力PBP2α

MRSA7种主要流行株大量地域性传播SCCmecⅠ-Ⅲ(HA-MRSA)－伴其他耐药元件－耐多药SCCmecⅣ(CA-MRSA)－不伴其他耐药元件－小而容易水平转移SCCmecSCCmecGeneticsandEvolution8(2008)747–763ⅠⅡⅢⅣⅤⅥⅦTypingmethodsforS.aureusPulsed-fieldgelelectrophoresis(PFGE)Multilocussequencetyping(MLST)spatypingSCCmectypingMultilocussequencetypingMLSTSequenceanalysisoffragmentsofsevenS.aureushousekeepinggenesarcC,aroE,glpF,gmk,pta,tpiandyqiLAnallelicprofileofthe7genesdefinetheS.aureuslineage-sequencetype(ST)TheputativeancestorofaCCistheSTwiththelargestnumberofsinglelocusvariants

(SLVs)Ingeneral,MLSTdisadvantagesthatitisexpensive,laboriousandtimeconsuming.TypingofthespalocusSingle-locussequencetypingtechniquehasbecomeincreasinglypopularDeterminesthesequencevariatio