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,2,流行病學(xué),年發(fā)病率十萬分之五，隨年齡增大發(fā)病率上升，我國年發(fā)病約58萬例。 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。,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，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。見下圖：,4,圖1、心內(nèi)膜炎發(fā)生步驟,5,表1 感染性心內(nèi)膜炎并發(fā)癥,Congestive heart failure 5060% AIMR TR Embolization 2025% Mitral Aortic valve CVA 15% 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 abscess,6,診 斷,關(guān)鍵是具有高度的臨床警惕性 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 feverplus 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,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1小時(shí)，每次血液20ml，動(dòng)脈血陽性率較高，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)陽性率較高。,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、人工瓣分離、瓣膜關(guān)閉不全 敏感性 特異性 TTE 46% 95% TEE 93% 96% 可疑病人一定要作TEE檢查,9,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IE 10%30% ， 預(yù)后好 心內(nèi)膜電極心內(nèi)膜炎,10,感染性心內(nèi)膜炎手術(shù)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.,11,感染性心內(nèi)膜炎微生物學(xué)革蘭氏陽性球菌,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。 常見鏈球菌：血鏈球菌、牛鏈球菌、變異鏈 球菌及腸鏈球菌,12,感染性心內(nèi)膜炎微生物學(xué)革蘭氏陽性球菌,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IE 1%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%。,13,感染性心內(nèi)膜炎微生物學(xué)革蘭氏陽性球菌,營養(yǎng)變異性鏈球菌（NVS）占IE 2%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%。,14,感染性心內(nèi)膜炎微生物學(xué)革蘭氏陽性球菌,葡萄球菌 占IE 30%40%，其中80%90%為凝固酶陽性金葡菌，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, 近年來自體瓣IE也增加，2/3為凝固酶陰性IE。,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，常發(fā)生于吸毒、人工瓣及肝硬化者， 病程短于6周。沙門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)。,16,感染性心內(nèi)膜炎微生物學(xué)革蘭氏陰性桿菌,其它少見革蘭氏陰性桿菌 包括嗜血桿菌、放線桿菌等，培養(yǎng)困難，需23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)。 革蘭氏陽性桿菌（棒狀桿菌）IE少見。,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%病例合并需氧菌，栓塞常見，病死率30%。 霉菌IE 好發(fā)于3類病人：吸毒 心內(nèi)直視手術(shù) 長期靜脈應(yīng)用抗菌素。主要為ICU病人。常見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。,18,血培養(yǎng)陰性IE,占IE 5%30%。原因?yàn)椋?右心系統(tǒng)IE IE晚期，病程超過23個(gè)月。 慢性病變伴發(fā)尿毒癥 室缺、PDA、起搏電極IE 致病菌生長緩慢如厭氧菌、嗜血桿菌、放線桿菌、營養(yǎng)變異性鏈球菌（NVS）等。 使用抗生素后培養(yǎng) 霉菌性IE 立克次體、支原體等,19,抗微生物治療,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 OR 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,20,抗微生物治療,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 OR 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,21,抗微生物治療,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 6 weeks for prosthetic OR 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,22,抗微生物治療,營養(yǎng)變異性鏈球菌（NVS）及青霉素高度耐藥者：萬古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周或萬古4周或頭孢曲松+萬古4周,23,腸球菌治療方案（一）,Regimen Dosage and route Duration Susceptible to penicillin,gentamicin,and vancomycin Ampicillin sodium 12g/24 h IV in 6 doses 46 weeks OR Penicillin G 18-30million U/24h either continuously or 6 doses 46 weeks PLUS Gentamicin 3 mg/kg per 24h IV/IM in 3 equal doses 46 weeks OR Vancomycin 30 mg/kg per 24h IV in 2 equally divided doses 6 weeks PLUS 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 46 weeks OR Penicillin G 18-30 million U/24h either continuously or 6 doses 46 weeks PLUS Streptomycin sulfate 15mg/kg per 24h IV/IM in 2 equal doses 46 weeks OR Vancomycin 30mg/kg per 24h IV in 2 equally divided doses 6 weeks PLUS Streptomycin sulfate 15mg/kg per 24h IV/IM in 2 equal doses 6 weeks,24,腸球菌治療方案（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 PLUS 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 PLUS Gentamicin 3mg/kg per 24h IV/IM in 3 equal doses 6 weeks Resistant to penicillin, aminoglycosides, and vanvomycin E.faecium (屎腸球菌） Linezolid(利鈉唑胺) 1200mg/24h IV/po in 2 equal doses 8weeks E.faecalis (糞腸球菌） Ceftriaxone sodium 2g/24h IV/IM in 1 doses 8weeks PLUS Ampicillin sodium 12g/24h IV in 6 doses 8weeks,25,葡萄球菌IE抗菌素應(yīng)用,TABLE 12. Oerview of therapy for endocarditis caused by staphylococcus Regimen Dosage and route Duration Methicillin-susceptible organisms(native valves) Nafcillin(新青) 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 Gentamicin 3mg/kg per 24h IV/IM in 2 or 3 doses 3-5 days Methicillin-resistant organisms(native valves) Vancomycin 30mg/kg per 24h in 2 equally divided doses 6 weeks,26,葡萄球菌IE抗菌素應(yīng)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 PLUS 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 PLUS Rifampin 900mg/24h IN/PO in 3 doses 6 weeks PLUS Gentamicin 3mg/kg per 24h IV/IM 2 or 3 equal doses 2 weeks,27,沙門氏菌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,28,流感嗜血桿菌、放線桿菌IE抗菌素應(yīng)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 OR Ciprofloxacin 1000mg/24h PO or 800mg/24h 4 weeks for native valve IV in equal doses 6 weeks for prosthetic,29,霉菌性IE治療方案,二性霉素B 12周 或 +手術(shù) 氟康唑（大扶康） 術(shù)后 氟康唑利福平68周,30,血培養(yǎng)陰性IE抗菌療法,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 PLUS Gentamicin sulfate 3mg/kg per 24h IV/IM in 3 doses 4-6 weeks PLUS Ciprofloxaxin（環(huán)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 PLUS Gentamicin sulfate 3mg/kg per 24h IV/IM in 3 doses 2 weeks PLUS Cefepime 6g/24h IV in 3 doses 6 weeks PLUS Rifampin 900mg/24h PO/IV in 3 doses 6 weeks,31,血培養(yǎng)陰性IE抗菌療法,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 PLUS Gentamicin sulfate 3mg/kg per 24h IV/IM in 3 doses 2 weeks OR Rifampin 600mg/24h IV/PO in 2 doses 2 weeks,32,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,33,預(yù) 防,TABLE 15. Prophylactic regimens for dental, oral, respiratory tract, or esophageal procedures(follow-up dose no longer redcommended) Standard general prophylaxis for patients at risk: Amoxicillin:Adults, 2.0g (children, 50mg/kg) given orally 1 hour before peocedure. Unable to take oral medications: Ampicillin: Adults, 2.0 g (children, 50mg/kg) given IM or IV within 30 minutes before procedure. Amoxicillin/ ampicillin/penicillin allergic patients: Clindamycin(克林霉素): Adults, 600mg (children, 20mg/kg) given orally 1 hour before peocedure. -OR- Cephalexin* (頭孢氨芐) or Cefadroxil*（頭孢羥氨芐）: Adults, 2.0 g (children 50mg/kg) orally 1 hour before peocedure. 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.,34,預(yù) 防,TABLE 16. Prophylactic regimens for genitourinary/gastrointestinal procedures .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. .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