葡萄球菌進(jìn)化及其感染變遷環(huán)境與蜥蜴進(jìn)化面對抗菌藥物的壓力，細(xì)菌的進(jìn)化是非?？斓?

細(xì)菌耐藥細(xì)菌進(jìn)化-耐藥與致病性改變感染表現(xiàn)特征回歸到抗菌藥物前時代葡萄球菌環(huán)境改變-主要是抗菌藥物應(yīng)用威脅健康者生命的感染近年細(xì)菌感染性疾病中，最難以預(yù)料的事件之一就是：迅速出現(xiàn)的CA-MRSA(community-associatedmethicillin-resistantStaphylococcusaureus)感染；CA-MRSA感染已成為健康人群所患疾病的首要原因。Pnas,2008;105:1327-1332葡萄球菌屬G+小球菌，兼性厭氧菌；目前發(fā)現(xiàn)有32種，寄生人體有16種，分凝固酶陽性與凝固酶陰性；主要寄居于皮膚和前鼻道，成年人攜帶率20%~50%，分為持續(xù)帶菌者、間歇帶菌者和從不帶菌者（分別為24%、57%和20%）；少數(shù)人可攜帶致病性葡萄球菌，醫(yī)務(wù)人員帶菌率高達(dá)70%，且多為耐藥性菌株。

凝固酶陽性

凝固酶陰性S.aureus

S.epidermidisS.saprophyticusS.haemolyticusS.warneriS.capitisS.hominisS.caprae

S.cohniiS.xylosusS.auricularisS.simulansS.schleiferiS.lugdunensisS.saccharolyticusS.pasteuri皮膚、粘膜表面的葡萄球菌葡萄球菌耐藥趨勢對青霉素耐藥：青霉素剛問世時（1940s），葡萄球菌對其異常敏感，成為葡萄球菌感染的“特效藥”(miracledrug)；第一位青霉素使用者，Oxfordshire警察，一年后，Rammelkamp確認(rèn)葡萄球菌對青霉素耐藥菌株；1946年，多達(dá)60%菌株產(chǎn)生青霉素酶，20年內(nèi)，高達(dá)80%醫(yī)院和社區(qū)分離的菌株對青霉素耐藥；耐藥由質(zhì)粒編碼的青霉素酶介導(dǎo)，并迅速在不同菌株中蔓延。為何對青霉素的耐藥產(chǎn)生如此迅速？致病性有改變嗎？50yearsagoMargaretPatriciaJevons,ofthePublicHealthLaboratoryServiceinColindale,London,publishedthefirstdescriptionofmeticillin-resistantStaphylococcusaureus(MRSA).耐藥菌株獲得了一個新的蛋白-PBP2a，其能阻止抗菌藥物與其他PBP的結(jié)合而發(fā)揮作用產(chǎn)生耐藥；編碼PBP2a的基因稱mecA，其位于葡萄球菌染色體盒mecA（StaphylococcalChromosomeCassettemec,SCCmec）上；SCCmec有7個亞型：typeⅠ~Ⅶ；MRSANCCLS(美國臨床實(shí)驗(yàn)室標(biāo)準(zhǔn)委員會)規(guī)定：葡萄球菌(金葡菌和凝固酶陰性葡萄球菌)對甲氧西林耐藥指對所有β-內(nèi)酰胺類抗生素耐藥對絕大多數(shù)大環(huán)內(nèi)酯類、氟喹諾酮類、氨基糖苷類等同時耐藥治療藥物應(yīng)首選糖肽類抗生素最初，MRSA完全與醫(yī)院或其它衛(wèi)生保健環(huán)境狀態(tài)下發(fā)生相關(guān)，稱為衛(wèi)生保健相關(guān)MRSA（healthcare-associatedMRSA,HA-MRSA)HA-MRSA主要引起醫(yī)療相關(guān)環(huán)境狀態(tài)下的bloodstreaminfections

和nosocomialpneumoniaHA-MRSA引起的感染逐年穩(wěn)步增加，不同地區(qū)增加趨勢有別Italy始于1980s初期；USA始于1980s后期；UK始于1990s；歐洲較晚，始于2005，北歐0%；南歐50%；2003，USA，在ICU葡萄球菌感染中，60%是MRSA；與5年前相比增加了11%?，F(xiàn)在，MRSA不僅三級醫(yī)療機(jī)構(gòu)與大學(xué)教學(xué)醫(yī)院常見，而且，在較小的醫(yī)療機(jī)構(gòu)同樣常見。社區(qū)獲得MRSA(CA-MRSA)偶爾引起的感染已報道多年，最初大多數(shù)患者存在可以識別的危險因素如接觸衛(wèi)生保健提供環(huán)境或腸道外途徑濫用藥品；現(xiàn)在的流行始于1990s的后期，無任何危險因素的健康者。

健康兒童致死性CA-MRSA感染(Case2)1998年1月，NorthDakota農(nóng)村16歲印第安女孩，因休克伴40.6℃、抽搐、彌漫性瘀斑和易怒住當(dāng)?shù)蒯t(yī)院；接著發(fā)生呼吸衰竭、心臟驟停，不到2小時死亡；死后立即抽血和腦脊液培養(yǎng)MRSA陽性，對多類抗菌藥物敏感；尸檢發(fā)現(xiàn)腦、心、肝和腎多發(fā)小膿腫，腦膜、血和肺組織培養(yǎng)MRSA陽性；1月前，因中耳炎服用amoxicillin，此前一年病人及家庭成員無住院史，家庭成員沒有住在LTCFs的，也沒有在衛(wèi)生保健部門工作的。JAMA,1999;282:1123-1125健康兒童致死性CA-MRSA感染(Case3)1999年1月，Minnesota農(nóng)村13歲白人女孩，因發(fā)熱、咯血和呼吸窘迫住當(dāng)?shù)蒯t(yī)院；第7天因腦水腫和多器官衰竭死亡；病人的血、痰和胸液培養(yǎng)MRSA陽性，對多類抗菌藥物敏感；尸檢發(fā)現(xiàn)左肺實(shí)變性出血性壞死；病人既往無慢性病、近期未住院、無IDU(injecting-druguse)史，家庭成員沒有住在LTCFs的，也沒有在衛(wèi)生保健部門工作的。JAMA,1999;282:1123-1125EurRespirJ2009;34:1470–1476CA-MRSAisusuallysusceptibletomostnon-β-lactamantibioticsCA-MRSA菌株為Ⅳ~Ⅴ亞型，新近出現(xiàn)Ⅶ亞型，常常攜帶編碼PVL的基因。HA-MRSA菌株多數(shù)為SCCmec亞型Ⅰ~Ⅲ，其很少攜帶編碼PVL的基因；最初僅在醫(yī)院環(huán)境感染中出現(xiàn)MRSA，后來演變?yōu)樵谏鐓^(qū)流行，即HA-MRSA進(jìn)化為CA-MRSA經(jīng)過一個歷史輪回現(xiàn)在，CA-MRSA又將從社區(qū)引向醫(yī)院最終……萬古霉素耐藥趨勢葡萄球菌對萬古霉素耐藥：萬古霉素作為治療MRSA最常用的抗生素已經(jīng)應(yīng)用近50年，但萬古霉素耐藥鮮有報道；1997年日本報道第一株VISA；2002年美國CDC報道世界上第一株VRSA；2004年亞洲耐藥致病菌監(jiān)測網(wǎng)顯示亞洲各國1350株MRSA中，僅58株（4.3%）為heteroVISA；我國尚無VRSA報道，但已有heteroVISA和VISA的個別報道。VRSA的前體實(shí)際上只是引起慢性感染（象皮膚潰瘍，其常與VRE相關(guān)）的單純的MRSA。隨著長期萬古霉素治療，通過質(zhì)粒交換從合并感染的VRE獲得萬古霉素耐藥基因（vanA），MRSA變?yōu)閂RSA。細(xì)菌初步突變獲得耐藥，同時可能出現(xiàn)生存和致病性的缺陷；其會通過突變補(bǔ)償機(jī)制克服這種缺陷達(dá)到完美的進(jìn)化，既耐藥又強(qiáng)治病，可怕！如何對應(yīng)？HA-MRSA的致病性Ininvasiveinfections,patientswithMRSAinfectionhadasignificantlyhighermortalitythandidthosewithMSSAinfection(pooledoddsratio[OR],1.93;95%confidenceinterval[CI],1.54–2.42;P<.001);CosgroveSE,SakoulasG,PerencevichEN,etal.Comparisonofmortalityassociatedwithmethicillin-resistantandmethicillin-susceptibleStaphylococcusaureusbacteremia:ameta-analysis.ClinInfectDis2003;36:53–9.

病死率高HA-MRSA的致病性Anincreasedlengthofhospitalstayandincreasedcostsattributabletomethicillinresistance;CosgroveSE,QiY,KayeKS,etal.TheimpactofmethicillinresistanceinStaphylococcusaureusbacteremiaonpatientoutcomes:mortality,lengthofstay,andhospitalcharges.InfectControlHospEpidemiol2005;26:166–74.

住院時長、費(fèi)用增加ManypotentialfactorsinthepathwaybetweenmethicillinresistanceandmortalityMRSAandMSSAstrainsareabletoproducesimilarlevelsofhemolysins,exfoliativetoxins,enterotoxins,toxicshocksyndrometoxin,lipase,nuclease,andprotease;SomestudieshaveshownthatcertainclinicalMRSAstrainsmayproducemoreexterotoxinAandBaswellascoagulase,comparedwithMSSA,butthesefindingsarenotconsistent.IsMRSAmorevirulentthanMSSA?ClinMicrobiolInfect2007;13:843–5.Enterotoxinandtoxicshocksyndrometoxin-1productionofmethicillinresistantandmethicillinsensitiveStaphylococcusaureusstrains.EurJEpidemiol1997;13:699–708.

Productionof‘‘virulencefactors’’by‘‘epidemic’’methicillin-resistantStaphylococcusaureusinvitro.JMedMicrobiol1989;30:245–52.Comparisonofenterotoxinsandhaemolysinsproducedbymethicillin-resistant(MRSA)andsensitive(MSSA)Staphylococcusaureus.JMedMicrobiol1992;36:164–71HA-MRSA的致病性并沒有增強(qiáng)Thisregion(calledSCCmec)isusuallylargeinhospital-acquiredMRSA(SCCmectypeIIII)andissmallerandpotentiallymoremobileinCA-MRSA(typicallySCCmectypesIVorV).Interestingly,itappearsthatthelargerelementresultsinasignificantfitnesscost,coupledwithareductionintoxinproduction.Community-associatedmethicillin-resistantStaphylococcusaureus:epidemiologyandclinicalconsequencesofanemergingepidemic.ClinMicrobiolRev2010;23:616–87.OffsettingvirulenceandantibioticresistancecostsbyMRSA.ISMEJ2010;4:577–84.HA-MRSA的生存力降低、毒素產(chǎn)生減少Themostlikelyexplanationsfortheexcessmortality,morbidity,andcostsassociatedwithMRSAinfectionaretheclinicalfactorsFirstDelayinreceivingeffectiveantibiotictherapyleadstoworsepatientoutcomes;PatientsinfectedwithMRSAaresignificantlymorelikelythanotherstoreceiveinactiveempiricalantibiotictherapy.SecondVancomycinuseforMSSAbacteremiawasassociatedwitha3.53-foldincreaseinmortalityrelativetocephazolin(95%CI,1.15–13.45).MortalityamongthosewithbacteremicMRSApneumoniatreatedwithvancomycin(50%)wassimilartomortalityamongthosewithMSSAinfectiontreatedwithvancomycin(47%)andthatbothoftheseweresignificantlyhigherthanmortalityamongthosewithMSSAtreatedwithaβ-lactam.Useofvancomycinorfirst-generationcephalosporinsforthetreatmentofhemodialysisdependentpatientswithmethicillin-susceptibleStaphylococcusaureusbacteremia.ClinInfectDis2007;44:190–6.BacteremicpneumoniaduetoStaphylococcusaureus:acomparisonofdiseasecausedbymethicillin-resistantandmethicillin-susceptibleorganisms.ClinInfectDis1999;29:1171–7.萬古霉素在MSSA感染及伴菌血癥MRSA肺炎的治療中沒有優(yōu)勢ThirdPatientswithMRSAinfectiontendtobesickerandolderandhavemorecomorbiditiesthanthosewithMSSA.間接表明HA-MRSA的致病性是減弱的Therefore,ratherthanvirulencepersebeingtheexplanation,patientandantibioticfactorsarethemostlikelyexplanationfortheobservedpooreroutcomeswithMRSAinfection.MRSAVAP臨床緩解更慢即便給于初始恰當(dāng)抗感染治療，72h發(fā)熱和低氧血癥緩解率：MRSAVAP-30%;MSSAVAP-93.3%;H.influnzaeVAP-100%;PseudomonasaeruginosaVAP-73%。葡萄球菌引起的肺炎抗生素前時代流感后發(fā)生的肺炎有80%-90%迅速死亡；死后尸檢發(fā)現(xiàn)肺出血和微小膿腫形成。1950s除發(fā)生于流感后，也見于無流感者；無流感的危險因素：心肺疾病、酗酒、糖尿?。凰劳雎剩耗贻p成年-20%；流感后-30-50%；伴菌血癥-83%。CA-MRSA的致病性AnimalstudiesindicatethatCA-MRSAstrains(specificallyUSA300)aremorevirulentthanaretraditionalhospital-acquiredMRSA.IntheUnitedStates,CA-MRSAhasbeenassociatedwithmoreseverediseaseandaworseclinicaloutcomethanhascommunity-acquiredMSSA.Evolutionofvirulenceinepidemiccommunity-associatedmethicillin-resistantStaphylococcusaureus.ProcNatlAcadSciUSA2009;106:5883–8.Epidemiologyandoutcomesofcommunity-associatedmethicillin-resistantStaphylococcusaureusinfection.JClinMicrobiol2007;45:1705–11.CA-MRSA產(chǎn)生更多毒素、疾病更嚴(yán)重EurRespirJ2009;34:1470–1476Necrotisingpneumoniaona)achestradiographandb)acomputedtomography(CT)scanobtainedonday3.TheCTscanshowsmultiplebilateralnodularandcavitylesions.Reproducedfrom[51]withpermissionfromthepublisher.EurRespirJ2009;34:1470–1476ThegenesencodingPanton-Valentineleukocidin(PVL)areenrichedinCAMRSAclones.PVL,whichisapotentpore-formingleukotoxinthatisrarely(,5%ofisolates)foundinhospitalacquiredMRSAandisonlyfoundin1%–10%ofMSSAisolatesbutisfrequentlydetectedinCA-MRSAisolates.PVLhasbeenlinkedwithmoresepsis,hemoptysis,leucopenia,necrotizinginfectionsofskinandmucosa,necrotizingpneumonitis,andhighermortalityinpatientswhohavecommunity-onsetS.aureuspneumonia.Wavesofresistance:Staphylococcusaureusintheantibioticera.NatRevMicrobiol2009;7:629–41.AssociationbetweenStaphylococcusaureusstrainscarryinggeneforPanton-Valentineleukocidinandhighlylethalnecrotisingpneumoniainyoungimmunocompetentpatients.Lancet2002;359:753–9.Severecommunity-acquiredpneumoniaduetoStaphylococcusaureus,2003–04influenzaseason.EmergInfectDis2006;12:894–9.InvolvementofPanton-Valentineleukocidin-producingStaphylococcusaureusinprimaryskininfectionsandpneumonia.ClinInfectDis1999;29:1128–32.PVL是CA-MRSA進(jìn)化獲得的、與嚴(yán)重的壞死性感染相關(guān)的主要毒素2009-11-232009-11-24產(chǎn)PVL的SA所致壞死性肺炎的致死預(yù)測因子根據(jù)重要的結(jié)果比較50例PVL陽性葡萄球菌壞死性肺炎患者的臨床和生物學(xué)特征及對應(yīng)的葡萄球菌分離菌株特征產(chǎn)PVL的SA所致壞死性肺炎的致死預(yù)測因子病死率：56%；中位生存時間：10days。致命性結(jié)果與以下三個經(jīng)典的疾病嚴(yán)重性因子相關(guān)：需要機(jī)械通氣；需要應(yīng)用血管活性藥物；發(fā)生ARDS。

氣道出血與致命性結(jié)果強(qiáng)烈相關(guān)。

白細(xì)胞減少是與死亡相關(guān)的主要生物學(xué)特征。入院后最初24h出現(xiàn)leukopenia和erythroderma與致死性結(jié)果獨(dú)立相關(guān)?？┭c預(yù)后Hemoptysis：壞死性肺炎的主要診斷特征，致死性結(jié)果的重要的預(yù)測因子；Airwayhemorrhage：反映呼吸道黏膜壞死，其是PVL直接毒性效應(yīng)的結(jié)果。咯血與預(yù)后ContrarytoPVL-negativeS.aureuspneumonia,PVL-positiveS.aureuspneumoniaisoftenprecededbyinfluenza-likesymptomsandismainlycharacterizedbyhemoptysis,pleuraleffusion,rapidonsetofacuterespiratorydistress,andleukopenia.

AssociationbetweenStaphylococcusaureusstrainscarryinggeneforPanton-Valentineleukocidinandhighlylethalnecrotisingpneumoniainyoungimmunocompetentpatients.Lancet2002;359:753–9Figure1ProbabilityofsurvivalamongpatientswithPanton-Valentineleukocidin–positiveStaphylococcusaureuspneumonia,accordingtoairwaybleeding.白細(xì)胞數(shù)與預(yù)后白細(xì)胞計數(shù)在生存者與死亡者間存在顯著差別；白細(xì)胞技術(shù)與死亡危險間似乎存在線性關(guān)系：WBC<1000/ml，生存率<10%；WBC>10000/ml，生存率>85%；

體外資料顯示PVL誘導(dǎo)人白細(xì)胞的凋亡和壞死。產(chǎn)PVL的SA所致壞死性肺炎的致死預(yù)測因子結(jié)論Airwaybleeding,erythroderma,andleukopeniaareassociatedwithfataloutcomefromPanton-Valentineleukocidin–positiveS.aureusnecrotizingpneumonia.PVL誘導(dǎo)肺炎癥和損傷的機(jī)制一種可能：PVL誘導(dǎo)PMN溶解，導(dǎo)致宿主防御受損，干擾了宿主對感染部位微生物的清除，未受抑制的微生物得以生長并表達(dá)其他組織損傷外毒素（如α溶血素）；另一種可能：PVL本身直接或間接引起組織損傷。PVL激活PMN，釋放促炎介質(zhì)（IL-8和LtB4）和顆粒酶（β葡萄糖苷酸酶、水解酶和溶菌酶），產(chǎn)生活性氧代謝物。Pore-formingandcytolyticactivitiesofPVLtowardhumanandrabbitPMNs.DiepBAetal.PNAS2010;107:5587-5592?2010byNationalAcademyofSciences(A)PMNporeformation[percentethidiumbromide(EtBr)-positivecells](B)PMNlysis[percentlactatedehydrogenase(LDH)release]assaysusingLukS-PVandLukF-PVpurifiedfromculturesupernatantsofaPVL-producingUSA300strainasdescribedinSIText.(C)Poreformationcausedby1:2,000dilutionsof8-hCCYculturesupernatantsofUSA300wild-typestrain,Δpvlmutant,andcompΔpvlstrainasindicated.

PVL并非預(yù)先形成的毒素LukS-PVwasproducedin12–18μgperlunginrabbitsinfectedwith6×109cfuofeitherwild-typeorcompΔpvlstrains;noLukS-PVwasdetectedinthelungsofrabbitsinfectedwiththeΔpvlstrain;PVLwasnotdetectedinthelungsofrabbitsinfectedwith1.5×109cfuofthewild-typestrain,indicatingthatahighbacterialburdenintherabbitlungisrequiredforPVLtobeproducedinamounts.Therefore,denovoPVLproductionduringinfection,notpreformedtoxin,wasresponsiblefortheincreasedvirulenceofwild-typeandcompΔpvlstrains.Time-courseofPVL-inducedacutelunginjuryafterendotrachealinstillationwithSF8300wild-type(wt)strain,isogenicΔpvlmutant,orvehiclecontrol.DiepBAetal.PNAS2010;107:5587-5592?2010byNationalAcademyofSciencesMechanismsofPVL-inducedacutelunginjuryandlunginflammation.DiepBAetal.PNAS2010;107:5587-5592?2010byNationalAcademyofSciencesAlthoughthesevirulencedeterminantsarenotuniquetoCA-MRSA,thelevelofexpressionappearstobeenhancedinsomeCA-MRSAstrainsthatcontributetomore-severedisease.alpha-hemolysinandtheα-typephenol-solublemodulinsIdentificationofnovelcytolyticpeptidesaskeyvirulencedeterminantsforcommunityassociatedMRSA.NatMed2007;13:1510–4.Poringoverpores:alpha-hemolysinandPanton-ValentineleukocidininStaphylococcusaureuspneumonia.NatMed2007;13:1405–6.溶血素能促進(jìn)PVL對PMN的PoringoverporesTheargininecatabolicmobileelement(ACME)TheACMEisuniquetoUSA300andcontains2potentialvirulencefactors,includinggenesencodinganargininedeiminasepathwayandanoligopeptidePermease.ACMEhasbeenshowntobeimportantforthefitnessofCA-MRSA(USA-300)inananimalmodel.CA-MRSA的生存力增強(qiáng)Theargininecatabolicmobileelementandstaphylococcalchromosomalcassettemeclinkage:convergenceofvirulenceandresistanceintheUSA300cloneofmethicillin-resistantStaphylococcusaureus.JInfectDis2008;197:1523–30.TheemergenceandspreadofMRSAinthecommunityhaschangedtheapproachtoempiricaltherapyforseriouscommunity-onsetinfections.

Today,anyseriousinfectionthatispotentiallycausedbystaphylococcishouldbepresumedtobeduetoMRSAuntilcultureresultsareavailable.EurRespirJ2009;34:1190–1196CA-MRSA的耐藥性較HA-MRSA減少，僅對頭孢菌素耐藥；CA-MRSA致病性更強(qiáng)。hVISA/VISA的致病性過去，hVISA/VISAinfectionsdescribedaconcerningpictureforpatients,includingprolongedbacteremia;more-complexdisease,suchasendocarditis,osteomyelitis,andprostheticdeviceinfections;vancomycintreatmentfailure;andincreasedmortality；現(xiàn)在，comparedwithMRSAstrains,anattenuatedvirulenceofhVISA/VISAstrainsweremorelikelytobecolonizers；MICof

vancomycin>1.5μg/mLhadasignificantlylowerriskofdeath

at3months,comparedwiththosewithavancomycinMIC<1.5μg/mL;TheriskofshockwasalsoshowntobesignificantlylowerinpatientsinfectedwithMRSAstrainsthathadavancomycinMICof2μg/mL,comparedwiththoseinfectedwithstrainswithlowerMICs;Areducedsystemicproinflammatoryresponsehasalsobeendescribedforthesepatientsinanotherstudy.統(tǒng)計方法改變：排除疾病嚴(yán)重性等影響因素ANTIMICROBALRESISTANCE.CID2011:53(15September):579hVISA/VISA的致病性Athickeningofthecellwallreducedsusceptibilitytovancomycin.NF-κBstimulationandcytokineproduction(tumornecrosisfactorαandinterleukin1β)havebeenshowntobesignificantlyreducedinVISAclinicalisolates.theinfectivityofVISAstrainsisupto100timeslowerthanisogenicvancomycinsusceptibleparentisolates.more-resistantVISAsubcloneshadagreaterdegreeofvirulenceattenuation,comparedwithsusceptibleparentisolatesBacterialsmallcolonyvariants(SCVs)werefirstdescribedin1910,asanaberrantformofEberthellatyphosa(nowknownasSalmonellaentericaserovarTyphi,S.typhi).SCVshavebeendescribedforawiderangeofbacterialgeneraandspecies,includingStaphylococcusaureus,meticillin(formerlymethicillin)-resistantS.aureus,Staphylococcusepidermidis,Staphylococcuscapitis,Pseudomonasaeruginosa,Burkholderiacepacia,Salmonellaserovars……NATUREREVIEWSICROBIOLOGYVOLUME4|APRIL2006|295SCV的致病性Small-ColonyVariant(SCV)strainsofS.aureusareclearlylinkedtoantimicrobialexposureandresistance.ThisisespeciallytrueforgentamicinandotheraminoglycosidesSmallcolonyvariants:apathogenicformofbacteriathatfacilitatespersistentandrecurrentinfections.NatRevMicrobiol2006;4:295–305.S.aureusSCVshavesignificantgrowthdefects:unusualcolonymorphology,reducedpigmentationandhemolysis,alteredbiochemicalreactivity.AkeyfeatureofS.aureusSCVsistheirpropensitytoinvadeandpersistinsidehostcells,suchasepithelialorendothelialcells,withoutstimulatingsignificanthostresponsesorinducingcelllysis.SCVstrainsofS.aureusarelessvirulentthanarewild-typeS.aureusSCV的特點(diǎn)SCV相關(guān)的疾病Cysticfibrosis.PatientswithCF,especiallychildrenandadolescents,areoftencolonizedwithS.aureus.Osteomyelitis