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1、感染性心内膜炎进展感染性心内膜炎进展及指南及指南宁波市医疗中心李惠利医院周建庆流行病学v年发病率十万分之五，随年龄增大发病率上升，我国年发病约58万例。v危险因素：人工瓣膜、风心、先心、老年退行性主动脉瓣病变、二尖瓣脱垂、介入治疗、血透、牙科手术、静脉留置。2病 理v3/4病人原有器质性心脏病基础。内皮细胞破坏，血小板及纤维蛋白积聚，细菌产生粘附基质分子，细菌粘附繁殖。见下图：3图1、心内膜炎发生步骤4表1 感染性心内膜炎并发症 Congestive heart failure 5060% AIMR TR Embolization 2025% Mitral Aortic valve CVA 1
2、5% Other emboli Limb 23% Mesenteric 2% Splenic 23% Glomerulonephritis 1525% Anular abscess 1015% Myocotic aneurysm 1015% Conduction system involvement 510% CNS abscess 34% Other less common complications 12% Pericarditis Myocarditis Myocardial infarction intracardiac fistula Metastatic abscess5诊 断 关
3、键是具有高度的临床警惕性关键是具有高度的临床警惕性Table5CriteriathatshouldraisesuspicionofIEHighclinicalsuspision(rugentindicationforechocardiographicscreeningandpossiblyhospitaladmission)newvalvelesion/(regurgitant)murmurembolicenent(s)ofunknownorigin(esp.cerebralandrenalinfarction)sepsisofunknownoriginhaematuria,goumerulo
4、nephritis,andsuspectedrenalinfarctionfeverplusprostheticmaterialinsidetheheartotherhighpredispositionsforIEnewlydevelopedventriculararrhythmiasorconductiondisturbancesfirstmanifestationofCHFpositiveBCs(iftheorganismidentifiedistypicalforNVE/PVE)cutaneous(Osler,Janeway)orophtahlmic(Roth)manifestation
5、smultifocal/rapidchangingpulmonicinfiltrations(righyheartIE)peripheralabscesses(renal,splenic,spine)ofunknownoriginpredispositionandrecentdiagnostic/theraputicinterventionsknowntoresultinsignificantbacteraemia6血培养方法 v抗生素应用前需3次以上血培养，间隔超过1小时，每次血液20ml，动脉血阳性率较高，分2种培养基：普通，厌氧。如已短期使用抗生素，病情稳定,停药3天后多次培养。如血培养
6、多次阴性，骨髓培养阳性率较高，洁尿培养也有一定价值，皮肤Osler小结节、脱落的赘生物及手术标本培养阳性率较高。 7感染性心内膜炎心超表现 v赘生物、脓肿、动脉瘤、窦道、瓣体穿孔、人工瓣分离、瓣膜关闭不全 v 敏感性 特异性 TTE 46% 95% TEE 93% 96% v可疑病人一定要作TEE检查8类 型 v自体瓣膜心内膜炎v人工瓣膜心内膜炎 5年发生率3%5%v 静脉吸毒者心内膜炎 右心系统好发 ， 占总IE 10%30% ， 预后好v 心内膜电极心内膜炎9感染性心内膜炎手术指征 TABLE9.Generalindicationsforsurgicalinterventionininfe
7、ctionsendocarditisEmergencysurgery(24hours)Aorticinsufficiencywithevidenceforsignificant(FC3)CHF.Ruptureofsinusofvalsalvaintoanothercardiacstructure.Fistulaformationintoanothercardiacstructureorpericardium.Urgentsurgery(2-4days)PresenceofFC3or4CHFduetovalvulardysfunction.Perivalrularabscessformation
8、.Prostheticvalvularobstruction.ProstheticvalvulardehiscenceEarlysurgery(4-10days)Persistentfeverfeltduetoendocarditis.Positivesurveillancecultures.Recurrentsepticemboli.Highlyresistantorvirulentorganism(fungi,Brucellae,Pseudomonas,antibiotic-resistantenterococci,poorlyresponsiveS.aureus)Large(10mm)m
9、obilevegetations,especiallyonthemitralvalve. Immediatelyreplaseaftercompletionofpriorendocarditistreatment. 10感染性心内膜炎微生物学革兰氏阳性球菌v链球菌 占IE约50%60% ，儿童及年轻妇女心内膜炎主要为草绿色链球菌，预后较好，90%能治愈，但30%以上可有并发症。 常见链球菌：血链球菌、牛链球菌、变异链 球菌及肠链球菌11感染性心内膜炎微生物学革兰氏阳性球菌v肠链球菌（肠球菌）为消化道及前尿道正常菌群，占IE的5%18%，常为亚急性过程。肠球菌血症常为医源性，多发生于尿道操作后的
10、老年人及妇科操作后的年轻女性，40%以上病人无原发心脏病基础，对许多抗菌素耐药，治愈困难，病死率高。v肺炎链球菌占IE 1%3%，常急性起病伴瓣环脓肿及急性化脓性心包炎，70%并发脑膜炎，由于急性瓣膜破坏引起血流动力学障碍，病死率高达50%。12感染性心内膜炎微生物学革兰氏阳性球菌v营养变异性链球菌（NVS）占IE 2%3%，常隐匿起病，有原发心脏病基础，血培养常阴性。治疗困难，预后不良。vB族链球菌 为口腔、生殖道、前尿道正常菌群。糖尿病、肝硬化、肿瘤等免疫力低下者为危险因素。病死率也高达50%。13感染性心内膜炎微生物学革兰氏阳性球菌v葡萄球菌 占IE 30%40%，其中80%90%为凝固
11、酶阳性金葡菌，侵犯正常瓣膜，常引起急性IE, 伴血行播散性脓肿，化脓性心包炎。v表皮葡萄球菌 常引起人工瓣IE, 近年来自体瓣IE也增加，2/3为凝固酶阴性IE。14感染性心内膜炎微生物学革兰氏阴性杆菌v革兰氏阴性杆菌少见，常发生于吸毒、人工瓣及肝硬化者， 病程短于6周。沙门氏菌常引起左心系统心内膜炎。假单胞菌属（包括绿脓杆菌）IE多发于吸毒者并侵犯正常瓣膜，常合并栓塞、瓣周脓肿、周围脓肿、急性心衰等并发症，需及早手术。15感染性心内膜炎微生物学革兰氏阴性杆菌v其它少见革兰氏阴性杆菌 包括嗜血杆菌、放线杆菌等，培养困难，需23周，临床表现相似：大而脆的赘生物、栓塞、返流、心衰等，需换瓣手术。v
12、革兰氏阳性杆菌（棒状杆菌）IE少见。16感染性心内膜炎微生物学v厌氧菌 主要为脆弱类杆菌IE，25%病例合并需氧菌，栓塞常见，病死率30%。v霉菌IE 好发于3类病人：吸毒 心内直视手术 长期静脉应用抗菌素。主要为ICU病人。常见为白色念珠菌及曲菌属，病死率86%，尽早手术是治疗的最好办法。v其它微生物如螺旋体、立克次体、衣原体及支原体等均可引起IE。17血培养阴性IE v 占IE 5%30%。原因为： 右心系统IE IE晚期，病程超过23个月。 慢性病变伴发尿毒症 室缺、PDA、起搏电极IE 致病菌生长缓慢如厌氧菌、嗜血杆菌、放线杆菌、营养变异性链球菌（NVS）等。 使用抗生素后培养 霉菌性
13、IE 立克次体、支原体等 18抗微生物治疗 TABLE 10. Overview of TABLE 10. Overview of therpytherpy for for endocarditisendocarditis caused by caused by viridansviridans group or group or streptococcus streptococcus bovisbovisRegimen Regimen Dosage and route Duration(per type of valve)Dosage and route Duration(per type
14、of valve) Highly penicillin-sensitive organismsHighly penicillin-sensitive organismsPenicillin G 12-18 million U/24 h either 4 weeks for native valve Penicillin G 12-18 million U/24 h either 4 weeks for native valve continuous or 4-6 doses 6 weeks for prosthetic continuous or 4-6 doses 6 weeks for p
15、rostheticORORCeftriaxoneCeftriaxone sodium 2 g/24 h IV/IM in 1 dose 4 weeks for native valve sodium 2 g/24 h IV/IM in 1 dose 4 weeks for native valve 6 weeks for prosthetic 6 weeks for prostheticORORPenicillin G plusPenicillin G plus GentamicinGentamicin Penicillin G 12-18 million U/24 h either 2 we
16、eks for native valve Penicillin G 12-18 million U/24 h either 2 weeks for native valve Continuous or 6 divided doses 6 weeks for prosthetic Continuous or 6 divided doses 6 weeks for prosthetic GentamicinGentamicin 3 mg/kg per 24h IV/IM in 1 dose 2 weeks for either 3 mg/kg per 24h IV/IM in 1 dose 2 w
17、eeks for either19抗微生物治疗Regimen Regimen Dosage and route Duration(per type of valve)Dosage and route Duration(per type of valve)ORORCeftriaxoneCeftriaxone sodium sodium plus plus gentamicingentamicin CeftriaxoneCeftriaxone 2 g/24 h IV/IM in 1 dose 2 weeks for native valve 2 g/24 h IV/IM in 1 dose 2 w
18、eeks for native valve 6 weeks for prosthetic 6 weeks for prosthetic GentamicinGentamicin 3 mg/kg per 24 h IV/IM in 1 dose 2 weeks for either 3 mg/kg per 24 h IV/IM in 1 dose 2 weeks for eitherORORVancomycinVancomycin 30mg/kg per 24 h in 2 equal doses 4 weeks for native valve 30mg/kg per 24 h in 2 eq
19、ual doses 4 weeks for native valve to maximum of 2 g/24 hrs 6 weeks for prosthetic to maximum of 2 g/24 hrs 6 weeks for prosthetic Relatively penicillin-resistant organismsRelatively penicillin-resistant organisms(Penicillin or (Penicillin or ceftriaxoneceftriaxone) plus ) plus gentamicingentamicin
20、Penicillin G 24million U/24 h either continuously 4 weeks for native valve Penicillin G 24million U/24 h either continuously 4 weeks for native valve Or 4-6 equally divided dose 6 weeks for prosthetic Or 4-6 equally divided dose 6 weeks for prosthetic20抗微生物治疗Regimen Regimen Dosage and route Duration
21、(per type of valve)Dosage and route Duration(per type of valve)OROR CeftriaxoneCeftriaxone 2 g/24 h IV/IM in 1 dose 4 weeks for native valve 2 g/24 h IV/IM in 1 dose 4 weeks for native valve 6 weeks for prosthetic 6 weeks for prosthetic PLUS PLUS GentamicinGentamicin 3 mg/kg per 24 h IV/IM in 1 dose
22、 2 weeks for native valve 3 mg/kg per 24 h IV/IM in 1 dose 2 weeks for native valve 6 weeks for prosthetic 6 weeks for prostheticORORVancomycinVancomycin 30 mg/kg per 24 h in 2 equal doses 4 weeks for native valve 30 mg/kg per 24 h in 2 equal doses 4 weeks for native valve to maximum of 2 g/24 h 6 w
23、eeks for prosthetic to maximum of 2 g/24 h 6 weeks for prosthetic 21抗微生物治疗v营养变异性链球菌（NVS）及青霉素高度耐药者：万古6周+庆大6周v肺炎链球菌：青霉素4周或头孢曲松4周v耐青霉素者：头孢噻肟4周或万古4周或头孢曲松+万古4周22肠球菌治疗方案（一）vRegimen Dosageandroute Duration v v Susceptible to penicillin,gentamicin,and vancomycinvAmpicillinsodium12g/24hIVin6doses46weeksvORvP
24、enicillinG18-30millionU/24heithercontinuouslyor6doses46weeksvPLUSvGentamicin3mg/kgper24hIV/IMin3equaldoses46weeksvORvVancomycin30mg/kgper24hIVin2equallydivideddoses6weeksvPLUSvGentamicin3mg/kgper24hIV/IMin3equaldoses6weeksv Susceptible to penicillin, streptomycin, vancomycin, but resistant to gentam
25、icinvAmipicillinsodium12g/24hIVin6doses46weeksvORvPenicillinG18-30millionU/24heithercontinuouslyor6doses46weeksvPLUSvStreptomycinsulfate15mg/kgper24hIV/IMin2equaldoses46weeksvORvVancomycin30mg/kgper24hIVin2equallydivideddoses6weeksvPLUSvStreptomycinsulfate15mg/kgper24hIV/IMin2equaldoses6weeks23肠球菌治疗
26、方案（二）v RegimenDosageandrouteDurationv Susceptible to aminoglycosides and vancomycin but resistant to penicillinvBeta-lactamase producing strainvAmpicillin-sulbactam(舒巴舒巴坦坦)12g/24hIVin4doses6weeksvPLUSvGentamicin3mg/kgper24hIV/IMin3equaldoses6weeksvORvVancomycin30mg/kgper24hIVin2equallydivideddoses6w
27、eeksvPLUSvGentamicin3mg/kgper24hIV/IMin3equaldoses6weeksvIntrinsic penicillin resistancevVancomycin30mg/kgper24hIVin2equallydivideddoses6weeksvPLUSvGentamicin3mg/kgper24hIV/IMin3equaldoses6weeksv vResistant to penicillin, aminoglycosides, and vanvomycinvE.faecium(屎肠球菌）屎肠球菌）vLinezolid(利钠唑胺利钠唑胺)1200mg
28、/24hIV/poin2equaldoses8weeksvE.faecalis(粪肠球菌）粪肠球菌）vCeftriaxonesodium2g/24hIV/IMin1doses8weeksvPLUSvAmpicillinsodium12g/24hIVin6doses8weeks24葡萄球菌IE抗菌素应用 TABLE12.OerviewoftherapyforendocarditiscausedbystaphylococcusRegimenDosageandrouteDurationMethicillin-susceptibleorganisms(nativevalves)Nafcillin(新青
29、新青)oroxacillin12g/24hIVin4-6doses6weeksWithoptionofgentamicinGentamicin3mg/kgper24hIV/IMin2or3doses3-5daysORCefazolinWithoptionofgentamicin6g/24hin3divideddoses6weeksGentamicin3mg/kgper24hIV/IMin2or3doses3-5daysMethicillin-resistantorganisms(nativevalves)Vancomycin30mg/kgper24hin2equallydivideddoses
30、6weeks25葡萄球菌IE抗菌素应用TABLE 12. TABLE 12. OerviewOerview of therapy for of therapy for endocarditisendocarditis caused by staphylococcus caused by staphylococcus Regimen Dosage and route DurationRegimen Dosage and route Duration Methicillin-susceptible organisms (prosthetic material)Methicillin-suscept
31、ible organisms (prosthetic material)NafcillinorNafcillinor oxacillinoxacillin 12g/24h IV in 4-6 doses 6 weeks 12g/24h IV in 4-6 doses 6 weeks PLUS PLUSRifampinRifampin 900mg/24h IV/PO in 3 doses 6 weeks 900mg/24h IV/PO in 3 doses 6 weeks PLUS PLUSGentamicinGentamicin 3mg/kg per 24h IV/IM in 2 or 3 e
32、qual doses 2 weeks 3mg/kg per 24h IV/IM in 2 or 3 equal doses 2 weeks Methicillin-resistant organisms (prosthetic material)Methicillin-resistant organisms (prosthetic material)VancomycinVancomycin 30mg/kg per 24h in 2 equal doses to 6 weeks 30mg/kg per 24h in 2 equal doses to 6 weeks maximum of 2g/2
33、4h maximum of 2g/24h PLUS PLUSRifampinRifampin 900mg/24h IN/PO in 3 doses 6 weeks 900mg/24h IN/PO in 3 doses 6 weeks PLUS PLUSGentamicinGentamicin 3mg/kg per 24h IV/IM 2 or 3 equal doses 2 weeks 3mg/kg per 24h IV/IM 2 or 3 equal doses 2 weeks 26沙门氏菌IE抗菌素应用 三代头孢或氨苄青霉素 6周 v +庆大霉素 2周 v 或链霉素 4周 v绿脓杆菌 妥布
34、霉素 8周v + v 替卡西林 8周v 或v 先锋必 8周v 27流感嗜血杆菌、放线杆菌IE抗菌素应用TABLE13.OverviewoftherapyforeithernativeorprostheticendocardiiticausedbyHACEKorganisemsRegimenDosageandrouteDurationCeftriaxonesodium2g/24hIV/IMin1dose4weeksORAmpicillin-sulbactam12gper24hIVin4equally4weeksdivideddosesORCiprofloxacin1000mg/24hPOor80
35、0mg/24h4weeksfornativevalveIVinequaldoses6weeksforprosthetic28霉菌性IE治疗方案 二性霉素B 12周 或 +手术 氟康唑（大扶康） 术后 氟康唑利福平68周29血培养阴性IE抗菌疗法 TABLE14.OverviewoftherapyforculturenegativenativeorprostheticendocarditisRegimenDosageandRouteDurationNativevalveAmpicillin-sulbactam12g/24hIVin4dose4-6weeksPLUSGentamicinsulfat
36、e3mg/kgper24hIV/IMin3doses4-6weeksORVancomycin30mg/kgIVin2doses4-6weeksPLUSGentamicinsulfate3mg/kgper24hIV/IMin3doses4-6weeksPLUSCiprofloxaxin（环丙沙星）（环丙沙星）1000mg/24hpoor800mg4-6weeksIVin2equaldosesProstheticvalve(early,1year)Vancomycin30mg/kgper24hIV/IMin2doses6weeksPLUSGentamicinsulfate3mg/kgper24hI
37、V/IMin3doses2weeksPLUSCefepime6g/24hIVin3doses6weeksPLUSRifampin900mg/24hPO/IVin3doses6weeks30血培养阴性IE抗菌疗法 RegimenDosageandRouteDurationProstheticvalve(late,1year)Suspectedbartonella.culturenegativeCeftriaxonesodium2g/24hIV/IMin1dose6weeksPLUSGentamicinsulfate3mg/kaper24hin3doses2weeksOPTINALDoxycycl
38、ine200mg/24hIV/POin2doses6weeksDocumentedbartonella.culturepositiveDoxycycline200mg/24hIV/POin2doses6weeksPLUSGentamicinsulfate3mg/kgper24hIV/IMin3doses2weeksORRifampin600mg/24hIV/POin2doses2weeks31预防 v高危患者：人工瓣膜 、曾是IE患者、紫绀型先心病、主肺动脉分流术后v中危患者：其它先心、获得型瓣膜病、肥厚性心肌病、二尖瓣脱垂、主动脉瓣退行性变32预 防vTABLE15.Prophylactic
39、regimensfordental,oral,respiratorytract,oresophagealprocedures(follow-updosenolongerredcommended)vStandardgeneralprophylaxisforpatientsatrisk:vAmoxicillin:Adults,2.0g(children,50mg/kg)givenorally1hourbeforepeocedure.vUnabletotakeoralmedications:vAmpicillin:Adults,2.0g(children,50mg/kg)givenIMorIVwit
40、hin30minutesbeforevprocedure.vAmoxicillin/ampicillin/penicillinallergicpatients:vClindamycin(克林霉素克林霉素):Adults,600mg(children,20mg/kg)givenorally1hourbeforevpeocedure.v-OR-vCephalexin*(头孢氨苄头孢氨苄)orCefadroxil*（头孢羟氨苄）头孢羟氨苄）:Adults,2.0g(children50mg/kg)vorally1hourbeforepeocedure.vAmoxicillin/ampicillin/
41、penicillinallergicpatientsunabletotakeoralmedications：vClindamycin(克林霉素克林霉素):Adults,600mg(children,20mg/kg)IVwithin30minutesbeforevpeocedure.-OR-vCefazolin*：Adults,1.0g(children25mg/kg)IMorIVwithin30minutesbeforeprocedure.v33预 防TABLE16.Prophylacticregimensforgenitourinary/gastrointestinalprocedures.
42、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
43、.High-riskpatientsallergictoampicillin/amoxicillin:Vancomycinplusgentamixcin1.5mg/kg(forbothadultsandchildren,nottoexceed120mg)IMorIV.Completeinjection/infusionwithin30minutesbeforestartingprocedure.Modetare-riskpatients:Amoxicillin:Adults,2.0g(children50mg/kg)orally1hourbeforeprocedure-OR-Ampicilli
44、n:Aduuls,2.0g(children50mg/kg)IMorIVwithin30minutesbeforestartingprocedure.Moderate-riskpatientsallergictoampicillin/amoxicillin:Vancomycin:adults,1.0g(children20mg/kg)IVover1-2hours.Completeinfusionwithin30minutesofstartingtheprocedure.34参考文献1.Baddour LM, Wilson WR, Bayer AS, et,al. AHA Scientific
45、Statement: Infective endocarditis:diagnosis,antimicrobial therapy, and management of complications: a statement for health-care professionals from the committee on Rheumatic Fever, Endocarditis,and Kawasaki Disease, Council on Clinical Cardiology, Stroke, and Cardiovascular surgery and anesthesia, A
46、merican Heart Associationececutive summary : endorsed by the Infectious Diseases Society of America.1.Circulation 2005;111(23):3167-84. 2.The Task Force Members, Dieter Horstkotte, Ferenc Follath, Erno Gutschik, et,al. Guidelines on Prevention, Diagnosis and Treatment of Infective EndocarditisExecutive Summary. Europe Heart Journal2004;25(3):267-276.3.Thomas M. Bashore, Christopher Cabell, Vacne Fowler. Update on Infective Endocarditis. Current problems in Cardiology. 2006,31(4):265-352.35 谢 谢 ！ 36
