上海交通大學(xué)醫(yī)學(xué)院新華兒童兒童醫(yī)學(xué)中心兒科學(xué)之ca-mrsa-091

MRSA感染趨勢和治療進(jìn)展上海市兒童醫(yī)院上海交通大學(xué)附屬兒童醫(yī)院呼吸科陸敏上海市兒童醫(yī)院ShanghaiChildren’sSTAPHYLOCOCCUSstaphyle-abunchofgrapeskokkus-berry金黃色葡萄球菌

StaphylococcusAureus1928所有葡萄球菌對青霉素敏感1942首次從病人別離耐青霉素的葡萄球菌1950‘s醫(yī)院內(nèi)耐青霉素葡萄球菌大流行頭孢霉素、紅霉素、萬古霉素1960甲氧西林耐青霉素酶1961首次在倫敦出現(xiàn)MRSA金黃色葡萄球菌耐藥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,February2021

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+全球耐藥狀況〔2005-2006)WangHetal.DiagnMicrobiolInfectDis2021;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，首次報道從靜脈吸毒者或經(jīng)常接觸護(hù)理機(jī)構(gòu)的高危人群種別離出MRSA80年代后期，首次報道從經(jīng)常接觸護(hù)理所的兒童中別離到MRSA1990‘s中期，芝加哥大學(xué)報道住院病人MRSA增加25倍1999年報道4例兒童死于致死性社區(qū)獲得性MRSA〔CA-MRSA〕感染，這些兒童并無MRSA易感因素CA-MRSA出現(xiàn)CA-MRSA定義多中心監(jiān)測顯示：社區(qū)獲得MRSA為12％美國郊區(qū)74％MRSA感染是社區(qū)獲得的，提示在這一地區(qū)MRSA已取代了MSSAmata分析顯示：總CA-MRSA發(fā)生率分別占住院MRSA病人的30.2％和37.3％1.3％的社區(qū)人群有MRSA定殖CA-MRSA2001-2002surveillanceinUS1647CA-MRSAinfection8-20%werenotassociatedwithtraditionalriskfactors-CA-MRSAMostwereassociatedwithclinicallyrelevantinfectionsthatrequiredtreatmentManypatientswerechildrenwhorequiredhospitalizationWashingtonPost.Retrievedon2007-10-19

Community-acquiredMRSAinAsiaANSORPSurveillanceinAsia-2005-6%局部亞洲國家MRSA發(fā)病率高于西方國家,占院內(nèi)金黃色葡萄球菌標(biāo)本的70％臺灣北部兒童CA-MRSA占CA-SA感染的74％。新加坡CA-MRSA非常少見我國MRSA占SA的60％以上上海兒童CA-MRSA占MRSA17%，占SA1%CA-MRSACA-MRSA特征CA-MRSA:WhatitdoesCA-MRSA：比MSSA引起更深、更侵襲性感染，尤其是壞死性肺炎CA-MRSA：比MSSA更多壞死性筋膜炎CA-MRSA：引起菌血癥并不很多CA-MRSA：更多引起反復(fù)感染皮膚軟組織感染SSTIs80%ofCA-MRSAinfectionsareSSTIs,Necroticskinlesionsarealsoacommonpresentationandareoftenincorrectlyattributedtobitesbybrownreclusespidersorotherinsects.Generally,CA-MRSASSTIsarenotlife-threateninginvasiveinfection(eg,bacteremia,necrotizingfasciitis)canbecomedifficulttotreatandevencausedeath.壞死性筋膜炎NecrotizingfasciitisUSA300,SCCmecIV危險因素:preMRSA,HepCvirusinfection,diabetes,currentorpastinjectiondruguse,cancer,andHIV皮膚軟組織感染SSTIsCA-MRSA7天嬰兒，激惹和迅速增多皮疹CA-MRSAMRSA壞死性筋膜炎MRSA壞死性筋膜炎蜂窩織炎〔短箭〕脂膜炎〔長箭〕筋膜炎〔箭頭〕革蘭氏陽性球菌植皮后2周MRSA壞死性筋膜炎常見于熱帶地區(qū)，溫帶地區(qū)也有增加，尤其HIVCA-MRSA可能成為化膿性肌炎常見的病原45previouslyhealthychildreninwhomepisodesofbacterialmyositisorpyomyositisoccurred,26ofthesechildren(57.8%)--SA15ofthesepatients(57.7%)--CA-MRSA化膿性肌炎Pyomyositis.MRSAOsteomyelitisNecrotizingpneumonia(CAP)Post–influenzavirusinfectionInfluenzalikeillness(Post–influenzapneumonia)15casesofMRSACAPfrom9states(CDC),2003-2004influenzaseason4deaths(fatalityrate,26.7%)MRSA肺炎MRSA肺炎后期MRSA肺炎后期膿毒癥

SepsisWithorwithoutWaterhouse-Friderichsensyndromein2005,3fatalcasesattributedtoSaureusinfectioninchildrenwerereported,2CA-MRSA14previouslyhealthychildrenpresentedwithseveresepsis,12hadCA-MRSAsepsisOthermanifestationsSuppurativelymphadenitis,ophthalmicinfections(preseptalcellulitis,lidabscess,conjunctivitis,cornealulcers〕otitismedia,sinusitis,food-borneGIillness分子生物學(xué)特征所有MRSA含SCCmec

攜帶的mecA基因mecA基因編碼78kDa低親和力PBP2α

MRSA7種主要流行株大量地域性傳播SCCmecⅠ-Ⅲ(HA-MRSA)

－伴其他耐藥元件－耐多藥SCCmecⅣ(CA-MRSA)

－不伴其他耐藥元件－小而容易水平轉(zhuǎn)移SCCmecSCCmecGeneticsandEvolution8(2021)747–763ⅠⅡⅢⅣⅤⅥⅦTypingmethodsforS.aureusPulsed-fieldgelelectrophoresis(PFGE)Multilocussequencetyping(MLST)spatypingSCCmectypingMultilocussequencetypingMLSTSequenceanalysisoffragmentsofsevenS.aureushousekeepinggenesarcC,aroE,glpF,gmk,pta,tpiandyqiLAnallelicprofileofthe7genesdefinetheS.aureuslineage-sequencetype(ST)TheputativeancestorofaCCistheSTwiththelargestnumberofsinglelocusvariants

(SLVs)Ingeneral,MLSTdisadvantagesthatitisexpensive,laboriousandtimeconsuming.TypingofthespalocusSingle-locussequencetypingtechniquehasbecomeincreasinglypopularDeterminesthesequencevariationofthepolymorphicregionXoftheS.aureusproteinA(spa)locusStaphType(RidomGmbH,Wu¨rzburg,Germany)Buttwodifferentnomenclaturesystems金黃色葡萄球菌蛋白Aspa葡萄球菌蛋白A是金黃色葡萄球菌細(xì)胞壁的一個組成局部，編碼蛋白A的基因Spa有3個不同區(qū)域〔Fc結(jié)合區(qū)、X區(qū)和C末端〕X區(qū)2～15個重復(fù)序列，其數(shù)目、特征和排列順序具有高度多態(tài)性，同時具有良好的重復(fù)性和穩(wěn)定性，因此可用于對不同菌株分型CA-MRSASCCmectypingMultiplexPCRassaymecAanddifferentlocionSCCmecItoIVstructureofthemeccomplexandthepresenceofthedifferentccrgenesamultiplexPCRassaythatisbasedontheamplificationofsixspecificlociwithintheJ1regionofSCCmectypeIVvariants,Panton–ValentineleukocidinPVL

Panton–Valentineleukocidin〔PVL〕是一種由lukS-PV和lukF-PV基因編碼的具有破壞白細(xì)胞和介導(dǎo)組織壞死的微孔形成毒素〔pore-formingtoxin〕通常SCCmecIV型MRSA有40–90%攜帶PVL基因,而SCCmecI–III型MRSA那么<5%與CA-MRSA感染嚴(yán)重程度和社區(qū)的傳播有關(guān)?？梢鸾】祪和湍贻p人皮膚和軟組織感染以及壞死性肺炎Panton-Valentineleukocidin(PVL)Boyle-VavraandDaum.LabInvest2007SurvivalofS.aureusPneumonia

CorrelationwithPanton-ValentineLeukocidin(PVL)GeneRubinsteinEetal.ClinInfectDis2021;46:S375-85.特征HA-MRSACA-MRSA影響人群醫(yī)院、保健所、養(yǎng)老院和居住者年長者、早產(chǎn)兒和免疫低下者社區(qū)健康年輕者，無MRSA危險因素身體密切接觸人群（囚犯、軍隊(duì)、運(yùn)動隊(duì)、部落人群）感染部位敗血癥和傷口感染，呼吸道和泌尿道癥狀性感染皮膚（膿腫、蜂窩織炎、癤、嚴(yán)重皮膚和軟組織感染），膿毒性休克和敗血癥，壞死性肺炎危險因素植入裝置、導(dǎo)管、血透、長期住院、長期抗生素使用，身體密切接觸、擦傷、公共衛(wèi)生條件差、傳播人傳人：衛(wèi)生保健人員環(huán)境傳病人：醫(yī)院儀器等人傳人：公用設(shè)施環(huán)境傳人：公用運(yùn)動設(shè)備生物學(xué)特征耐甲氧西林耐其他抗生素