感染性心內(nèi)膜炎進(jìn)展及指南寧波市醫(yī)療中心李惠利醫(yī)院周建慶1感染性心內(nèi)膜炎進(jìn)展及指南寧波市醫(yī)療中心李惠利醫(yī)院1流行病學(xué)年發(fā)病率十萬(wàn)分之五，隨年齡增大發(fā)病率上升，我國(guó)年發(fā)病約5~8萬(wàn)例。危險(xiǎn)因素：人工瓣膜、風(fēng)心、先心、老年退行性主動(dòng)脈瓣病變、二尖瓣脫垂、介入治療、血透、牙科手術(shù)、靜脈留置。2流行病學(xué)年發(fā)病率十萬(wàn)分之五，隨年齡增大發(fā)病率上升，我國(guó)年發(fā)病病理3/4病人原有器質(zhì)性心臟病基礎(chǔ)。內(nèi)皮細(xì)胞破壞，血小板及纖維蛋白積聚，細(xì)菌產(chǎn)生粘附基質(zhì)分子，細(xì)菌粘附繁殖。見(jiàn)下圖：3病理3/4病人原有器質(zhì)性心臟病基礎(chǔ)。內(nèi)皮細(xì)胞破壞圖1、心內(nèi)膜炎發(fā)生步驟4圖1、心內(nèi)膜炎發(fā)生步驟4表1感染性心內(nèi)膜炎并發(fā)癥

Congestiveheartfailure50~60%AI＞MR＞TREmbolization20~25%Mitral＞AorticvalveCVA15%OtheremboliLimb2~3%Mesenteric2%Splenic2~3%Glomerulonephritis15~25%Anularabscess10~15%Myocoticaneurysm10~15%Conductionsysteminvolvement5~10%CNSabscess3~4%Otherlesscommoncomplications1~2%PericarditisMyocarditisMyocardialinfarctionintracardiacfistulaMetastaticabscess5表1感染性心內(nèi)膜炎并發(fā)癥

5診斷

關(guān)鍵是具有高度的臨床警惕性Table5CriteriathatshouldraisesuspicionofIE●

Highclinicalsuspision(rugentindicationforechocardiographicscreeningandpossiblyhospitaladmission)○newvalvelesion/(regurgitant)murmur○embolicenent(s)ofunknownorigin(esp.cerebralandrenalinfarction)○sepsisofunknownorigin○haematuria,goumerulonephritis,andsuspectedrenalinfarction○‘fever’plus█prostheticmaterialinsidetheheart█otherhighpredispositionsforIE█newlydevelopedventriculararrhythmiasorconductiondisturbances█firstmanifestationofCHF█positiveBCs(iftheorganismidentifiedistypicalforNVE/PVE)█cutaneous(Osler,Janeway)orophtahlmic(Roth)manifestations█multifocal/rapidchangingpulmonicinfiltrations(righyheartIE)█peripheralabscesses(renal,splenic,spine)ofunknownorigin█predispositionandrecentdiagnostic/theraputicinterventionsknowntoresultinsignificantbacteraemia6診斷關(guān)鍵是具有高度的臨床警惕性6血培養(yǎng)方法抗生素應(yīng)用前需3次以上血培養(yǎng)，間隔超過(guò)1小時(shí)，每次血液20ml，動(dòng)脈血陽(yáng)性率較高，分2種培養(yǎng)基：普通，厭氧。如已短期使用抗生素，病情穩(wěn)定,停藥3天后多次培養(yǎng)。如血培養(yǎng)多次陰性，骨髓培養(yǎng)陽(yáng)性率較高，潔尿培養(yǎng)也有一定價(jià)值，皮膚Osler小結(jié)節(jié)、脫落的贅生物及手術(shù)標(biāo)本培養(yǎng)陽(yáng)性率較高。7血培養(yǎng)方法抗生素應(yīng)用前需3次以上血培養(yǎng)，間隔超過(guò)1小時(shí)，每感染性心內(nèi)膜炎心超表現(xiàn)贅生物、膿腫、動(dòng)脈瘤、竇道、瓣體穿孔、人工瓣分離、瓣膜關(guān)閉不全

敏感性特異性TTE46%95%TEE93%96%

可疑病人一定要作TEE檢查8感染性心內(nèi)膜炎心超表現(xiàn)贅生物、膿腫、動(dòng)脈瘤、竇道、瓣體穿孔類型自體瓣膜心內(nèi)膜炎人工瓣膜心內(nèi)膜炎5年發(fā)生率3%~5%靜脈吸毒者心內(nèi)膜炎右心系統(tǒng)好發(fā)，占總IE10%~30%，預(yù)后好心內(nèi)膜電極心內(nèi)膜炎9類型自體瓣膜心內(nèi)膜炎9感染性心內(nèi)膜炎手術(shù)指征

TABLE9.GeneralindicationsforsurgicalinterventionininfectionsendocarditisEmergencysurgery(24hours)Aorticinsufficiencywithevidenceforsignificant(FC3)CHF.Ruptureofsinusofvalsalvaintoanothercardiacstructure.Fistulaformationintoanothercardiacstructureorpericardium.Urgentsurgery(2-4days)PresenceofFC3or4CHFduetovalvulardysfunction.Perivalrularabscessformation.Prostheticvalvularobstruction.ProstheticvalvulardehiscenceEarlysurgery(4-10days)Persistentfeverfeltduetoendocarditis.Positivesurveillancecultures.Recurrentsepticemboli.Highlyresistantorvirulentorganism(fungi,Brucellae,Pseudomonas,antibiotic-resistantenterococci,poorlyresponsiveS.aureus)Large(＞10mm)mobilevegetations,especiallyonthemitralvalve.

Immediatelyreplaseaftercompletionofpriorendocarditistreatment.10感染性心內(nèi)膜炎手術(shù)指征TABLE9.Gene感染性心內(nèi)膜炎微生物學(xué)－革蘭氏陽(yáng)性球菌鏈球菌占IE約50%~60%，兒童及年輕婦女心內(nèi)膜炎主要為草綠色鏈球菌，預(yù)后較好，90%能治愈，但30%以上可有并發(fā)癥。常見(jiàn)鏈球菌：血鏈球菌、牛鏈球菌、變異鏈球菌及腸鏈球菌11感染性心內(nèi)膜炎微生物學(xué)－革蘭氏陽(yáng)性球菌11感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陽(yáng)性球菌腸鏈球菌（腸球菌）為消化道及前尿道正常菌群，占IE的5%~18%，常為亞急性過(guò)程。腸球菌血癥常為醫(yī)源性，多發(fā)生于尿道操作后的老年人及婦科操作后的年輕女性，40%以上病人無(wú)原發(fā)心臟病基礎(chǔ)，對(duì)許多抗菌素耐藥，治愈困難，病死率高。肺炎鏈球菌占IE1%~3%，常急性起病伴瓣環(huán)膿腫及急性化膿性心包炎，70%并發(fā)腦膜炎，由于急性瓣膜破壞引起血流動(dòng)力學(xué)障礙，病死率高達(dá)50%。12感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陽(yáng)性球菌腸鏈球菌（腸球菌）為消感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陽(yáng)性球菌營(yíng)養(yǎng)變異性鏈球菌（NVS）占IE2%~3%，常隱匿起病，有原發(fā)心臟病基礎(chǔ)，血培養(yǎng)常陰性。治療困難，預(yù)后不良。B族鏈球菌為口腔、生殖道、前尿道正常菌群。糖尿病、肝硬化、腫瘤等免疫力低下者為危險(xiǎn)因素。病死率也高達(dá)50%。13感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陽(yáng)性球菌營(yíng)養(yǎng)變異性鏈球菌（NV感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陽(yáng)性球菌葡萄球菌占IE30%~40%，其中80%~90%為凝固酶陽(yáng)性金葡菌，侵犯正常瓣膜，常引起急性IE,伴血行播散性膿腫，化膿性心包炎。表皮葡萄球菌常引起人工瓣IE,近年來(lái)自體瓣IE也增加，2/3為凝固酶陰性IE。14感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陽(yáng)性球菌葡萄球菌占IE3感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陰性桿菌革蘭氏陰性桿菌少見(jiàn)，常發(fā)生于吸毒、人工瓣及肝硬化者，病程短于6周。沙門(mén)氏菌常引起左心系統(tǒng)心內(nèi)膜炎。假單胞菌屬（包括綠膿桿菌）IE多發(fā)于吸毒者并侵犯正常瓣膜，常合并栓塞、瓣周膿腫、周圍膿腫、急性心衰等并發(fā)癥，需及早手術(shù)。15感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陰性桿菌革蘭氏陰性桿菌少見(jiàn)，常感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陰性桿菌其它少見(jiàn)革蘭氏陰性桿菌包括嗜血桿菌、放線桿菌等，培養(yǎng)困難，需2~3周，臨床表現(xiàn)相似：大而脆的贅生物、栓塞、返流、心衰等，需換瓣手術(shù)。革蘭氏陽(yáng)性桿菌（棒狀桿菌）IE少見(jiàn)。16感染性心內(nèi)膜炎微生物學(xué)—革蘭氏陰性桿菌其它少見(jiàn)革蘭氏陰性桿菌感染性心內(nèi)膜炎微生物學(xué)厭氧菌主要為脆弱類桿菌IE，25%病例合并需氧菌，栓塞常見(jiàn)，病死率30%。霉菌IE好發(fā)于3類病人：①吸毒②心內(nèi)直視手術(shù)③長(zhǎng)期靜脈應(yīng)用抗菌素。主要為ICU病人。常見(jiàn)為白色念珠菌及曲菌屬，病死率86%，盡早手術(shù)是治療的最好辦法。其它微生物如螺旋體、立克次體、衣原體及支原體等均可引起IE。17感染性心內(nèi)膜炎微生物學(xué)厭氧菌主要為脆弱類桿菌IE，25%血培養(yǎng)陰性IE占IE5%~30%。原因?yàn)椋孩儆倚南到y(tǒng)IE②IE晚期，病程超過(guò)2~3個(gè)月。③慢性病變伴發(fā)尿毒癥④室缺、PDA、起搏電極IE⑤致病菌生長(zhǎng)緩慢如厭氧菌、嗜血桿菌、放線桿菌、營(yíng)養(yǎng)變異性鏈球菌（NVS）等。⑥使用抗生素后培養(yǎng)⑦霉菌性IE⑧立克次體、支原體等18血培養(yǎng)陰性IE占IE5%~30%。原因?yàn)椋孩儆倚南到y(tǒng)抗微生物治療

TABLE10.OverviewoftherpyforendocarditiscausedbyviridansgrouporstreptococcusbovisRegimen

DosageandrouteDuration(pertypeofvalve)

Highlypenicillin-sensitiveorganismsPenicillinG12-18millionU/24heither4weeksfornativevalvecontinuousor4-6doses6weeksforprostheticORCeftriaxonesodium2g/24hIV/IMin1dose4weeksfornativevalve6weeksforprostheticORPenicillinGplusGentamicinPenicillinG12-18millionU/24heither2weeksfornativevalveContinuousor6divideddoses6weeksforprostheticGentamicin3mg/kgper24hIV/IMin1dose2weeksforeither19抗微生物治療TABLE10.Overviewoft抗微生物治療Regimen

DosageandrouteDuration(pertypeofvalve)ORCeftriaxonesodiumplusgentamicinCeftriaxone2g/24hIV/IMin1dose2weeksfornativevalve6weeksforprostheticGentamicin3mg/kgper24hIV/IMin1dose2weeksforeitherORVancomycin30mg/kgper24hin2equaldoses4weeksfornativevalvetomaximumof2g/24hrs6weeksforprosthetic

Relativelypenicillin-resistantorganisms(Penicillinorceftriaxone)plusgentamicinPenicillinG24millionU/24heithercontinuously4weeksfornativevalveOr4-6equallydivideddose6weeksforprosthetic20抗微生物治療Regimen抗微生物治療Regimen

DosageandrouteDuration(pertypeofvalve)ORCeftriaxone2g/24hIV/IMin1dose4weeksfornativevalve6weeksforprostheticPLUSGentamicin3mg/kgper24hIV/IMin1dose2weeksfornativevalve6weeksforprostheticORVancomycin30mg/kgper24hin2equaldoses4weeksfornativevalvetomaximumof2g/24h6weeksforprosthetic21抗微生物治療Regimen抗微生物治療營(yíng)養(yǎng)變異性鏈球菌（NVS）及青霉素高度耐藥者：萬(wàn)古6周+慶大6周肺炎鏈球菌：青霉素4周或頭孢曲松4周耐青霉素者：頭孢噻肟4周或萬(wàn)古4周或頭孢曲松+萬(wàn)古4周22抗微生物治療營(yíng)養(yǎng)變異性鏈球菌（NVS）及青霉素高度耐藥者：萬(wàn)腸球菌治療方案（一）Regimen

Dosageandroute

Duration

Susceptibletopenicillin,gentamicin,andvancomycinAmpicillinsodium12g/24hIVin6doses4~6weeksORPenicillinG18-30millionU/24heithercontinuouslyor6doses4~6weeksPLUSGentamicin3mg/kgper24hIV/IMin3equaldoses4~6weeksORVancomycin30mg/kgper24hIVin2equallydivideddoses6weeksPLUSGentamicin3mg/kgper24hIV/IMin3equaldoses6weeks

Susceptibletopenicillin,streptomycin,vancomycin,butresistanttogentamicinAmipicillinsodium12g/24hIVin6doses4~6weeksORPenicillinG18-30millionU/24heithercontinuouslyor6doses4~6weeksPLUSStreptomycinsulfate15mg/kgper24hIV/IMin2equaldoses4~6weeksORVancomycin30mg/kgper24hIVin2equallydivideddoses6weeksPLUSStreptomycinsulfate15mg/kgper24hIV/IMin2equaldoses6weeks23腸球菌治療方案（一）Regimen腸球菌治療方案（二）

RegimenDosageandrouteDuration

SusceptibletoaminoglycosidesandvancomycinbutresistanttopenicillinBeta-lactamaseproducingstrainAmpicillin-sulbactam(舒巴坦)12g/24hIVin4doses6weeksPLUSGentamicin3mg/kgper24hIV/IMin3equaldoses6weeksORVancomycin30mg/kgper24hIVin2equallydivideddoses6weeksPLUSGentamicin3mg/kgper24hIV/IMin3equaldoses6weeksIntrinsicpenicillinresistanceVancomycin30mg/kgper24hIVin2equallydivideddoses6weeksPLUSGentamicin3mg/kgper24hIV/IMin3equaldoses6weeks

Resistanttopenicillin,aminoglycosides,andvanvomycinE.faecium

(屎腸球菌）Linezolid(利鈉唑胺)1200mg/24hIV/poin2equaldoses≥8weeksE.faecalis(糞腸球菌）Ceftriaxonesodium2g/24hIV/IMin1doses≥8weeksPLUSAmpicillinsodium12g/24hIVin6doses≥8weeks24腸球菌治療方案（二）

Regimen葡萄球菌IE抗菌素應(yīng)用

TABLE12.Oerviewoftherapyforendocarditiscausedbystaphylococcus

RegimenDosageandrouteDuration

Methicillin-susceptibleorganisms(nativevalves)Nafcillin(新青Ⅲ)oroxacillin12g/24hIVin4-6doses6weeksWithoptionofgentamicinGentamicin3mg/kgper24hIV/IMin2or3doses3-5daysORCefazolinWithoptionofgentamicin6g/24hin3divideddoses6weeksGentamicin3mg/kgper24hIV/IMin2or3doses3-5days

Methicillin-resistantorganisms(nativevalves)Vancomycin30mg/kgper24hin2equallydivideddoses6weeks

25葡萄球菌IE抗菌素應(yīng)用TABLE12.Oerview葡萄球菌IE抗菌素應(yīng)用TABLE12.Oerviewoftherapyforendocarditiscausedbystaphylococcus

RegimenDosageandrouteDuration

Methicillin-susceptibleorganisms(prostheticmaterial)Nafcillinoroxacillin12g/24hIVin4-6doses≥6weeksPLUSRifampin900mg/24hIV/POin3doses≥6weeksPLUSGentamicin3mg/kgper24hIV/IMin2or3equaldoses2weeks

Methicillin-resistantorganisms(prostheticmaterial)Vancomycin30mg/kgper24hin2equaldosesto≥6weeksmaximumof2g/24hPLUSRifampin900mg/24hIN/POin3doses≥6weeksPLUSGentamicin3mg/kgper24hIV/IM2or3equaldoses2weeks

26葡萄球菌IE抗菌素應(yīng)用TABLE12.Oerviewo沙門(mén)氏菌IE抗菌素應(yīng)用三代頭孢或氨芐青霉素6周+慶大霉素2周或鏈霉素4周綠膿桿菌妥布霉素8周+替卡西林8周或先鋒必8周

27沙門(mén)氏菌IE抗菌素應(yīng)用三代頭孢或氨芐青霉素流感嗜血桿菌、放線桿菌IE抗菌素應(yīng)用TABLE13.OverviewoftherapyforeithernativeorprostheticendocardiiticausedbyHACEKorganisemsRegimenDosageandrouteDurationCeftriaxonesodium2g/24hIV/IMin1dose4weeksORAmpicillin-sulbactam12gper24hIVin4equally4weeksdivideddosesORCiprofloxacin1000mg/24hPOor800mg/24h4weeksfornativevalveIVinequaldoses6weeksforprosthetic28流感嗜血桿菌、放線桿菌IE抗菌素應(yīng)用TABLE13.Ov霉菌性IE治療方案二性霉素B1~2周或+手術(shù)氟康唑（大扶康）

術(shù)后氟康唑＋利福平6～8周29霉菌性IE治療方案二性霉素B1~2周29血培養(yǎng)陰性IE抗菌療法

TABLE14.Overviewoftherapyforculturenegativenativeorprostheticendocarditis

RegimenDosageandRouteDuration

NativevalveAmpicillin-sulbactam12g/24hIVin4dose4-6weeksPLUSGentamicinsulfate3mg/kgper24hIV/IMin3doses4-6weeksORVancomycin30mg/kgIVin2doses4-6weeksPLUSGentamicinsulfate3mg/kgper24hIV/IMin3doses4-6weeksPLUSCiprofloxaxin（環(huán)丙沙星）1000mg/24hpoor800mg4-6weeksIVin2equaldoses

Prostheticvalve(early,＜1year)Vancomycin30mg/kgper24hIV/IMin2doses6weeksPLUSGentamicinsulfate3mg/kgper24hIV/IMin3doses2weeksPLUSCefepime6g/24hIVin3doses6weeksPLUSRifampin900mg/24hPO/IVin3doses6weeks30血培養(yǎng)陰性IE抗菌療法TABLE14.Overview血培養(yǎng)陰性IE抗菌療法

RegimenDosageandRouteDuration

Prostheticvalve(late,＞1year)Suspectedbartonella.culturenegativeCeftriaxonesodium2g/24hIV/IMin1dose6weeksPLUSGentamicinsulfate3mg/kaper24hin3doses2weeksOPTINALDoxycycline200mg/24hIV/POin2doses6weeksDocumentedbartonella.culturepositiveDoxycycline200mg/24hIV/POin2doses6weeksPLUSGentamicinsulfate3mg/kgper24hIV/IMin3doses2weeksORRifampin600mg/24hIV/POin2doses2weeks31血培養(yǎng)陰性IE抗菌療法Regimen預(yù)防高?；颊撸喝斯ぐ昴?、曾是IE患者、紫紺型先心病、主肺動(dòng)脈分流術(shù)后中?；颊撸浩渌刃摹@得型瓣膜病、肥厚性心肌病、二尖瓣脫垂、主動(dòng)脈瓣退行性變32預(yù)防高危患者：人工瓣膜、曾是IE患者、紫紺型先心病、主肺預(yù)防TABLE15.Prophylacticregimensfordental,oral,respiratorytract,oresophagealprocedures(follow-updosenolongerredcommended)

ⅠStandardgeneralprophylaxisforpatientsatrisk:Amoxicillin:Adults,2.0g(children,50mg/kg)givenorally1hourbeforepeocedure.ⅡUnabletotakeoralmedications:Ampicillin:Adults,2.0g(children,50mg/kg)givenIMorIVwithin30minutesbeforeprocedure.ⅢAmoxicillin/ampicillin/penicillinallergicpatients:Clindamycin(克林霉素):Adults,600mg(children,20mg/kg)givenorally1hourbeforepeocedure.-OR-Cephalexin*(頭孢氨芐)orCefadroxil*（頭孢羥氨芐）:Adults,2.0g(children50mg/kg)orally1hourbeforepeocedure.ⅣAmoxicillin/ampicillin/penicillinallergicpatientsunabletotakeoralmedications：Clindamycin(克林霉素):Adults,600mg(children,20mg/kg)IVwithin30minutesbeforepeocedure.-OR-Cefazolin*：Adults,1.0g(children25mg/kg)IMorIVwithin30minutesbeforeprocedure.

33預(yù)防TABLE15.Prophylactic預(yù)防TABLE16.Prophylacticregimensforgenitourinary/gastrointestinalproceduresⅠ.High-riskpatients:Ampicillinplusgentamicin:Ampicillin(adults,2.0g;chikdren50mg/kg)plusgentamicin1.5mg/kg(forbothadultsandchildren,nottoexceed120mg)IMorIVwithin30minutesbeforestartingpeocedure.6hourslater,ampicillin(adults,1.0g;children,25mg/kg)IMorIV,oramoxilillin(adults,1.0g;children,25mg/kg)orally.Ⅱ.High-riskpatientsallergictoampicillin/amoxicillin:Vancomycinplusgentamixcin1.5mg/kg(forbothadultsandchildren,nottoexceed120mg)IMorIV.Completeinjection/infusionwithin30minutesbeforestartingprocedure.Ⅲ.Modetare-riskpatients:Amoxicillin:Adults,2.0g(children50mg/kg)orally1hourbeforeprocedure-OR-Ampicillin:Aduuls,2.0g(children50mg/kg)IMorIVwithin30minutesbeforestartingprocedure.Ⅳ.Moderate-riskpatientsallergictoampicillin/amoxicillin:Vancomycin:adults,1.0g(children20mg/kg)IVover1-2hours.Completeinfusionwithin30minutesofstartingtheprocedure.34預(yù)防TABLE16.Prophylactic參考文獻(xiàn)BaddourLM,WilsonWR,BayerAS,et,al.AHAScientificStatement:Infectiveendocarditis:diagnosis,antimicrobialtherapy,andmanagementofcomplications:astatementforhealth-careprofessionalsfromthecommitteeonRheumaticFever,Endocarditis,andKawasakiDisease,CouncilonClinicalCardiology,Stroke,andCardiovascularsurgeryandanesthesia,AmericanHeartAssociation—ececutivesummary:endorsedbytheInfectiousDiseasesSocietyofAmerica.1.Circulation2005;111(23):3167-84.TheTaskForceMembers,DieterHorstkotte,FerencFollath,ErnoGutschik,et,al.GuidelinesonPrevention,DiagnosisandTreatmentofInfectiveEndocarditis—ExecutiveSummary.EuropeHeartJournal2004;25(3):267-276.ThomasM.Bashore,ChristopherCabell,VacneFowler.UpdateonInfectiveEndocarditis.CurrentproblemsinCardiology.2006,31(4):265-352.35參考文獻(xiàn)BaddourLM,WilsonWR,Bay謝謝！

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Congestiveheartfailure50~60%AI＞MR＞TREmbolization20~25%Mitral＞AorticvalveCVA15%OtheremboliLimb2~3%Mesenteric2%Splenic2~3%Glomerulonephritis15~25%Anularabscess10~15%Myocoticaneurysm10~15%Conductionsysteminvolvement5~10%CNSabscess3~4%Otherlesscommoncomplications1~2%PericarditisMyocarditisMyocardialinfarctionintracardiacfistulaMetastaticabscess43表1感染性心內(nèi)膜炎并發(fā)癥

5診斷

關(guān)鍵是具有高度的臨床警惕性Table5Criteriathatshoul