感染性心内膜炎进展及指南 宁波市医疗中心李惠利医院 周建庆

流行病学 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5~8万例。 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。

病 理 3/4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：

图1、心内膜炎发生步骤

表1 感染性心内膜炎并发症 AI＞MR ＞TR Embolization 20~25% Mitral ＞Aortic valve Congestive heart failure 50~60% AI＞MR ＞TR Embolization 20~25% Mitral ＞Aortic valve CVA 15% Other emboli Limb 2~3% Mesenteric 2% Splenic 2~3% Glomerulonephritis 15~25% Anular abscess 10~15% Myocotic aneurysm 10~15% Conduction system involvement 5~10% CNS abscess 3~4% Other less common complications 1~2% Pericarditis Myocarditis Myocardial infarction intracardiac fistula Metastatic abscess 7

诊 断 关键是具有高度的临床警惕性 Table 5 Criteria that should raise suspicion of IE 诊 断 关键是具有高度的临床警惕性 Table 5 Criteria that should raise suspicion of IE ● High clinical suspision (rugent indication for echocardiographic screening and possibly hospital admission) ○ new valve lesion/(regurgitant)murmur ○ embolic enent(s) of unknown origin (esp.cerebral and renal infarction) ○ sepsis of unknown origin ○ haematuria, goumerulonephritis, and suspected renal infarction ○ ‘fever’plus █ prosthetic material inside the heart █ other high predispositions for IE █ newly developed ventricular arrhythmias or conduction disturbances █ first manifestation of CHF █ positive BCs(if the organism identified is typical for NVE/PVE) █ cutaneous (Osler, Janeway) or ophtahlmic (Roth) manifestations █ multifocal/rapid changing pulmonic infiltrations(righy heart IE) █ peripheral abscesses(renal, splenic, spine)of unknown origin █ predisposition and recent diagnostic/theraputic interventions known to result in significant bacteraemia

血培养方法 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。

感染性心内膜炎心超表现 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 敏感性 特异性 TTE 46% 95% 敏感性 特异性 TTE 46% 95% TEE 93% 96% 可疑病人一定要作TEE检查

类 型 自体瓣膜心内膜炎 人工瓣膜心内膜炎 5年发生率3%~5% 静脉吸毒者心内膜炎 右心系统好发 ， 占总IE 10%~30% ， 预后好 类 型 自体瓣膜心内膜炎 人工瓣膜心内膜炎 5年发生率3%~5% 静脉吸毒者心内膜炎 右心系统好发 ， 占总IE 10%~30% ， 预后好 心内膜电极心内膜炎

感染性心内膜炎手术指征 TABLE 9.General indications for surgical intervention in infections endocarditis Emergency surgery (24 hours) Aortic insufficiency with evidence for significant (FC 3) CHF. Rupture of sinus of valsalva into another cardiac structure. Fistula formation into another cardiac structure or pericardium. Urgent surgery(2-4 days) Presence of FC 3 or 4 CHF due to valvular dysfunction. Perivalrular abscess formation. Prosthetic valvular obstruction. Prosthetic valvular dehiscence Early surgery (4-10 days) Persistent fever felt due to endocarditis. Positive surveillance cultures. Recurrent septic emboli. Highly resistant or virulent organism (fungi, Brucellae, Pseudomonas, antibiotic-resistant enterococci, poorly responsive S.aureus) Large(＞10mm) mobile vegetations, especially on the mitral valve. Immediately replase after completion of prior endocarditis treatment.

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。 感染性心内膜炎微生物学－革兰氏阳性球菌 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

感染性心内膜炎微生物学—革兰氏阳性球菌 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。 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%。

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。 感染性心内膜炎微生物学—革兰氏阳性球菌 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。 B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%。

葡萄球菌 占IE 30%~40%，其中80%~90%为凝固酶阳性金葡菌，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。 感染性心内膜炎微生物学—革兰氏阳性球菌 葡萄球菌 占IE 30%~40%，其中80%~90%为凝固酶阳性金葡菌，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。 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。

感染性心内膜炎微生物学—革兰氏阴性杆菌 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。

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2~3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。 感染性心内膜炎微生物学—革兰氏阴性杆菌 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2~3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。 革兰氏阳性杆菌（棒状杆菌）IE少见。

感染性心内膜炎微生物学 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%。 霉菌IE 好发于3类病人：①吸毒 ②心内直视手术 ③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。 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。

血培养阴性IE 占IE 5%~30%。原因为：① 右心系统IE ② IE晚期，病程超过2~3个月。③ 慢性病变伴发尿毒症 ④ 室缺、PDA、起搏电极IE ⑤ 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。⑥ 使用抗生素后培养 ⑦ 霉菌性IE ⑧ 立克次体、支原体等

抗微生物治疗 TABLE 10. Overview of therpy for endocarditis caused by viridans group or streptococcus bovis Regimen Dosage and route Duration(per type of valve) Highly penicillin-sensitive organisms Penicillin G 12-18 million U/24 h either 4 weeks for native valve continuous or 4-6 doses 6 weeks for prosthetic OR Ceftriaxone sodium 2 g/24 h IV/IM in 1 dose 4 weeks for native valve 6 weeks for prosthetic Penicillin G plus Gentamicin Penicillin G 12-18 million U/24 h either 2 weeks for native valve Continuous or 6 divided doses 6 weeks for prosthetic Gentamicin 3 mg/kg per 24h IV/IM in 1 dose 2 weeks for either

抗微生物治疗 OR Ceftriaxone sodium plus gentamicin Regimen Dosage and route Duration(per type of valve) OR Ceftriaxone sodium plus gentamicin Ceftriaxone 2 g/24 h IV/IM in 1 dose 2 weeks for native valve 6 weeks for prosthetic Gentamicin 3 mg/kg per 24 h IV/IM in 1 dose 2 weeks for either Vancomycin 30mg/kg per 24 h in 2 equal doses 4 weeks for native valve to maximum of 2 g/24 hrs 6 weeks for prosthetic Relatively penicillin-resistant organisms (Penicillin or ceftriaxone) plus gentamicin Penicillin G 24million U/24 h either continuously 4 weeks for native valve Or 4-6 equally divided dose 6 weeks for prosthetic

抗微生物治疗 Regimen Dosage and route Duration(per type of valve) OR Ceftriaxone 2 g/24 h IV/IM in 1 dose 4 weeks for native valve 6 weeks for prosthetic PLUS Gentamicin 3 mg/kg per 24 h IV/IM in 1 dose 2 weeks for native valve Vancomycin 30 mg/kg per 24 h in 2 equal doses 4 weeks for native valve to maximum of 2 g/24 h 6 weeks for prosthetic

抗微生物治疗 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 肺炎链球菌：青霉素4周或头孢曲松4周 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

肠球菌治疗方案（一） Regimen Dosage and route Duration Susceptible to penicillin,gentamicin,and vancomycin Ampicillin sodium 12g/24 h IV in 6 doses 4~6 weeks OR Penicillin G 18-30million U/24h either continuously or 6 doses 4~6 weeks PLUS Gentamicin 3 mg/kg per 24h IV/IM in 3 equal doses 4~6 weeks Vancomycin 30 mg/kg per 24h IV in 2 equally divided doses 6 weeks Gentamicin 3mg/kg per 24h IV/IM in 3 equal doses 6 weeks Susceptible to penicillin, streptomycin, vancomycin, but resistant to gentamicin Amipicillin sodium 12 g/24h IV in 6 doses 4~6 weeks Penicillin G 18-30 million U/24h either continuously or 6 doses 4~6 weeks Streptomycin sulfate 15mg/kg per 24h IV/IM in 2 equal doses 4~6 weeks Vancomycin 30mg/kg per 24h IV in 2 equally divided doses 6 weeks Streptomycin sulfate 15mg/kg per 24h IV/IM in 2 equal doses 6 weeks

肠球菌治疗方案（二） Regimen Dosage and route Duration Susceptible to aminoglycosides and vancomycin but resistant to penicillin Beta-lactamase producing strain Ampicillin-sulbactam(舒巴坦) 12g/24h IV in 4 doses 6 weeks PLUS Gentamicin 3mg/kg per 24h IV/IM in 3 equal doses 6 weeks OR Vancomycin 30mg/kg per 24h IV in 2 equally divided doses 6 weeks Gentamicin 3mg/kg per 24h IV/IM in 3 equal doses 6 weeks Intrinsic penicillin resistance Vancomycin 30mg/kg per 24h IV in 2 equally divided doses 6 weeks Gentamicin 3mg/kg per 24h IV/IM in 3 equal doses 6 weeks Resistant to penicillin, aminoglycosides, and vanvomycin E.faecium (屎肠球菌） Linezolid(利钠唑胺) 1200mg/24h IV/po in 2 equal doses ≥8weeks E.faecalis (粪肠球菌） Ceftriaxone sodium 2g/24h IV/IM in 1 doses ≥8weeks Ampicillin sodium 12g/24h IV in 6 doses ≥8weeks

葡萄球菌IE抗菌素应用 TABLE 12. Oerview of therapy for endocarditis caused by staphylococcus Regimen Dosage and route Duration Methicillin-susceptible organisms(native valves) Nafcillin(新青Ⅲ) or oxacillin 12g/24h IV in 4-6 doses 6 weeks With option of gentamicin Gentamicin 3mg/kg per 24h IV/IM in 2 or 3 doses 3-5 days OR Cefazolin With option of gentamicin 6g/24h in 3 divided doses 6 weeks Methicillin-resistant organisms(native valves) Vancomycin 30mg/kg per 24h in 2 equally divided doses 6 weeks  

葡萄球菌IE抗菌素应用 TABLE 12. Oerview of therapy for endocarditis caused by staphylococcus Regimen Dosage and route Duration Methicillin-susceptible organisms (prosthetic material) Nafcillinor oxacillin 12g/24h IV in 4-6 doses ≥6 weeks PLUS Rifampin 900mg/24h IV/PO in 3 doses ≥6 weeks Gentamicin 3mg/kg per 24h IV/IM in 2 or 3 equal doses 2 weeks Methicillin-resistant organisms (prosthetic material) Vancomycin 30mg/kg per 24h in 2 equal doses to ≥6 weeks maximum of 2g/24h Rifampin 900mg/24h IN/PO in 3 doses ≥6 weeks Gentamicin 3mg/kg per 24h IV/IM 2 or 3 equal doses 2 weeks  

沙门氏菌IE抗菌素应用 三代头孢或氨苄青霉素 6周 +庆大霉素 2周 或链霉素 4周 绿脓杆菌 妥布霉素 8周 + 替卡西林 8周 或 三代头孢或氨苄青霉素 6周 +庆大霉素 2周 或链霉素 4周 绿脓杆菌 妥布霉素 8周 + 替卡西林 8周 或 先锋必 8周

流感嗜血杆菌、放线杆菌IE抗菌素应用 TABLE 13. Overview of therapy for either native or prosthetic endocardiiti causedby HACEK organisems Regimen Dosage and route Duration Ceftriaxone sodium 2g/24h IV/IM in 1 dose 4 weeks OR Ampicillin-sulbactam 12g per 24h IV in 4 equally 4 weeks divided doses Ciprofloxacin 1000mg/24h PO or 800mg/24h 4 weeks for native valve IV in equal doses 6 weeks for prosthetic

霉菌性IE治疗方案 二性霉素B 1~2周 或 +手术 氟康唑（大扶康） 术后 氟康唑＋利福平6～8周

血培养阴性IE抗菌疗法 TABLE 14. Overview of therapy for culture negative native or prosthetic endocarditis Regimen Dosage and Route Duration Native valve Ampicillin-sulbactam 12g/24h IV in 4 dose 4-6 weeks PLUS Gentamicin sulfate 3mg/kg per 24h IV/IM in 3 doses 4-6 weeks OR Vancomycin 30mg/kg IV in 2 doses 4-6 weeks Ciprofloxaxin（环丙沙星） 1000mg/24h po or 800mg 4-6 weeks IV in 2 equal doses Prosthetic valve(early, ＜1 year) Vancomycin 30mg/kg per 24h IV/IM in 2 doses 6 weeks Gentamicin sulfate 3mg/kg per 24h IV/IM in 3 doses 2 weeks Cefepime 6g/24h IV in 3 doses 6 weeks Rifampin 900mg/24h PO/IV in 3 doses 6 weeks

血培养阴性IE抗菌疗法 Regimen Dosage and Route Duration Prosthetic valve (late,＞1 year) Suspected bartonella. culture negative Ceftriaxone sodium 2g/24h IV/IM in 1 dose 6 weeks PLUS Gentamicin sulfate 3mg/ka per 24h in 3 doses 2 weeks OPTINAL Doxycycline 200mg/24h IV/PO in 2 doses 6 weeks Documented bartonella. culture positive Doxycycline 200mg/24h IV/PO in 2 doses 6 weeks Gentamicin sulfate 3mg/kg per 24h IV/IM in 3 doses 2 weeks OR Rifampin 600mg/24h IV/PO in 2 doses 2 weeks

预防 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 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

预 防 TABLE 15. Prophylactic regimens for dental, oral, respiratory tract, or esophageal procedures(follow-up dose no longer redcommended) Ⅰ Standard general prophylaxis for patients at risk: Amoxicillin:Adults, 2.0g (children, 50mg/kg) given orally 1 hour before peocedure. Ⅱ Unable to take oral medications: Ampicillin: Adults, 2.0 g (children, 50mg/kg) given IM or IV within 30 minutes before procedure. Ⅲ Amoxicillin/ ampicillin/penicillin allergic patients: Clindamycin(克林霉素): Adults, 600mg (children, 20mg/kg) given orally 1 hour before peocedure. -OR- Cephalexin* (头孢氨苄) or Cefadroxil*（头孢羟氨苄）: Adults, 2.0 g (children 50mg/kg) orally 1 hour before peocedure. Ⅳ Amoxicillin/ ampicillin/penicillin allergic patients unable to take oral medications： Clindamycin(克林霉素): Adults, 600mg (children, 20mg/kg) IV within 30 minutes before peocedure.-OR- Cefazolin*：Adults, 1.0 g (children 25 mg/kg) IM or IV within 30 minutes before procedure.

预 防 TABLE 16. Prophylactic regimens for genitourinary/gastrointestinal procedures Ⅰ.High-risk patients: Ampicillin plus gentamicin: Ampicillin(adults,2.0g;chikdren 50mg/kg) plus gentamicin 1.5mg/kg(for both adults and children, not to exceed 120 mg) IM or IV within 30 minutes before starting peocedure. 6 hours later, ampicillin(adults, 1.0g;children,25 mg/kg) IM or IV, or amoxilillin (adults,1.0g; children, 25mg/kg) orally. Ⅱ.High-risk patients allergic to ampicillin/amoxicillin: Vancomycin plus gentamixcin 1.5mg/kg(for both adults and children, not to exceed 120 mg) IM or IV. Complete injection/infusion within 30 minutes before starting procedure. Ⅲ.Modetare-risk patients: Amoxicillin: Adults, 2.0g(children 50mg/kg) orally 1 hour before procedure-OR- Ampicillin: Aduuls, 2.0g(children 50mg/kg) IM or IV within 30 minutes before Ⅳ.Moderate-risk patients allergic to ampicillin/amoxicillin: Vancomycin: adults, 1.0g (children 20mg/kg) IV over 1-2 hours. Complete infusion within 30 minutes of starting the procedure.

参考文献 Baddour LM, Wilson WR, Bayer AS, et,al. AHA Scientific 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, American Heart Association—ececutive summary : endorsed by the Infectious Diseases Society of America.1.Circulation 2005;111(23):3167-84. The Task Force Members, Dieter Horstkotte, Ferenc Follath, Erno Gutschik, et,al. Guidelines on Prevention, Diagnosis and Treatment of Infective Endocarditis—Executive Summary. Europe Heart Journal2004;25(3):267-276. Thomas M. Bashore, Christopher Cabell, Vacne Fowler. Update on Infective Endocarditis. Current problems in Cardiology. 2006,31(4):265-352.

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