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-091

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首次从病人别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,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+全球耐药状况〔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，首次报道从静脉吸毒者或经常接触护理机构的高危人群种别离出MRSA80年代后期，首次报道从经常接触护理所的儿童中别离到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%局部亚洲国家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%)MRSA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(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金黄色葡萄球菌蛋白Aspa葡萄球菌蛋白A是金黄色葡萄球菌细胞壁的一个组成局部，编码蛋白A的基因Spa有3个不同区域〔Fc结合区、X区和C末端〕X区2～15个重复序列，其数目、特征和排列顺序具有高度多态性，同时具有良好的重复性和稳定性，因此可用于对不同菌株分型CA-MRSASCCmectypingMultiplexPCRassaymecAanddifferentlocionSCCmecItoIVstructureofthemeccomplexandthepresenceofthedifferentccrgenesamultiplexPCRassaythatisbasedontheamplificationofsixspecificlociwithintheJ1regionofSCCmectypeIVvariants,Panton–ValentineleukocidinPVL

Panton–Valentineleukocidin〔PVL〕是一种由lukS-PV和lukF-PV基因编码的具有破坏白细胞和介导组织坏死的微孔形成毒素〔pore-formingtoxin〕通常SCCmecIV型MRSA有40–90%携带PVL基因,而SCCmecI–III型MRSA那么<5%与CA-MRSA感染严重程度和社区的传播有关。可引起健康儿童和年轻人皮肤和软组织感染以及坏死性肺炎Panton-Valentineleukocidin(PVL)Boyle-VavraandDaum.LabInvest2007SurvivalofS.aureusPneumonia

CorrelationwithPanton-ValentineLeukocidin(PVL)GeneRubinsteinEetal.ClinInfectDis2021;46:S375-85.特征HA-MRSACA-MRSA影响人群医院、保健所、养老院和居住者年长者、早产儿和免疫低下者社区健康年轻者，无MRSA危险因素身体密切接触人群（囚犯、军队、运动队、部落人群）感染部位败血症和伤口感染，呼吸道和泌尿道症状性感染皮肤（脓肿、蜂窝织炎、疖、严重皮肤和软组织感染），脓毒性休克和败血症，坏死性肺炎危险因素植入装置、导管、血透、长期住院、长期抗生素使用，身体密切接触、擦伤、公共卫生条件差、传播人传人：卫生保健人员环境传病人：医院仪器等人传人：公用设施环境传人：公用运动设备生物学特征耐甲氧西林耐其他抗生素