Case Discussion A 65-year-old man was admitted due to intermittent fever for 3 months and progressive shortness of breath for half a month. Brief History The patient had been well until Dec. 2001, when he suffered from intermittent high fever after visiting a dental clinic for periodontitis. The fever initially subsided after taking some drugs from a clinic but recurred several days later. In January 2002, he started to have generalized myalgia & both hands arthralgia. Abdominal pain over LUQ developed in the early Feb. 2002; he visited a community hospital where spleen infarction was suspected after a CT scan. Splenectomy was performed on Feb. 17, of which pathology revealed massive hemorrhage with suppurative inflammation and neutrophil infiltration. One week after operation, fever recurred and associated with dyspnea, generalized arthralgia, anorexia, night sweats, and significant weight loss (6 kg/3 months). Due to deterioration of dyspnea, he visited an ER of a university hospital where a CXR showed cardiomegaly with lung congestion (Figure 1 ). He was admitted under the impression of congestive heart failure on March 5, 2002. The patient denied drug abuse or prostitute exposure. He was a heavy smoker before but quitted for one year. His occupation is a taxi driver. He had been to Mainland China eight years ago and no other travel history since that time. On physical examination, the patient appeared tired but not acutely ill. His consciousness was clear and oriented. The blood pressure was 130/90 mmHg. The temperature was 37.4 ℃, the pulse rate was 105 /min, and the respiration rate was 25/min. The head was normal, and the conjunctivae were mild pale. The sclerae were not icteric. The neck was supple without lymphadenopathy. The jugular vein was engorged. The breath sounds were bilateral basal crackles. The heart beats were regular with a Gr.II/VI systolic murmur over left upper sternal border and S3 gallop. The abdomen was soft and flat; no tenderness or rebound tenderness was noted. The liver was not palpable. The extremities moved freely without edema or petechiae. Laboratory Data 1. CBC/DC   WBC(K/μL) RBC(M/μL) HB(g/dL) MCV(fL) PLT(K/μL) Seg(%) Lym(%) Eos(%) 3/5 14.17  2.95 9.3 100.3 114 84.6 10.7 4.2 3/7 49.91 3.27 10.2 101.5 125 94.1 2.5 0.2 2. ABG   pH PaCO2(mmHg) PaO2(mmHg) HCO3-(mEq/L) B.E(mEq/L) FiO2 Ventilator Mode 3/5 7.531 19.6 144.5 16.5 -3.4 0.4 O2 cannula 3. BCS   T-Bil(mg/dL) D-Bil(mg/dL) AST(U/L) ALT(U/L) BUN(mg/dL) Cre(mg/dL) CK(U/L) 3/5 1.71 0.5 58.0 22.0 50.0 0.85   3/7 2.84 1.82 3546 1589 63.1 3.61 1504.0   Na(mmole/L) K(mmole/L) Cl(mmole/L) CRP(mg/dL) LDH(U/L) Lactic acid(mmole/L) 3/5 141.0 4.5 103.0 2.3     3/7 142.0 5.39 101.1 >12 2560 >12 4. Coagulation profile   PT PTT 3/7 24.6/12.4 65.4/37.1 5. Urinalysis   Sp. Gr pH protein Glu Keton Urobil O.B. RBC WBC Cast 3/5 1.005 5.0 30 - - - 3+ 20-25 0-2 Hy-Gr (3-5) Clincial course & treatment After admission, progressive dyspnea with impending respiratory failure was noted. He was intubated and transferred to ICU on March 7. Hypotension was noted and dopamine & dobutamine were administered. Intravenous furosemide was given for oligouria. Empirical antibiotic of ceftriaxone, penicillin-G and minocycline were given. Two days later, Janeway lesions were noted at acral part of four extremities. Transesophageal echocardiography showed vegetations on aortic valve (Figure 2 ) and severe aortic regurigatation. Subacute Infective endocarditis was diagnosed. Blood cultures yielded Streptococcus mitis in three sets and antibiotics were shifted to ceftriaxone and penicillin-G. He started to wean from ventilator and extubation was performed on March 9, 2002. Slurred speech was noted and embolic stroke was suspected. Brain MRI showed multiple small acute infarcts. Cardiovascular surgeon was consulted and operation was not suggested. Paroxysmal atrial fibrillation occurred in the noon on March 10 and intravenous amiodarone was given. Severe dyspnea with consciousness change was noted in the afternoon of March 10. Blood gas showed severe metabolic acidosis. Refractory hypotension occurred. Emergent operation was performed in the morning of March 11. Operation findings showed severe destruction of aortic valve (Figure 3) with perforation (Figure 4 ). After operation, he was transferred to surgical ICU for further management. 案例分析 本案例是一位細菌性心內膜炎的病人，病程進行到最後心臟衰竭及敗血性休克。整個病程可為三個階段：第一階段為明顯感染徵候期，病人此時有持續性發燒不退，白血球偏高，雖經藥物治療只能得到暫時緩解；病人此時發生了脾臟梗塞的現象，這是一個很重要需要鑑別診斷的問題，一般來說原因有三種：(1) 血液學疾病，如淋巴瘤、白血病及鐮刀型貧血；(2) 血栓栓塞問題，如敗血性栓塞、動脈阻塞；(3) 肉芽瘤（granuloma）或不明原因。病人經脾臟切除後，其病理切片結果顯示為化膿性變化，且有明顯白血球浸潤現象，這些都暗示著有細菌性的感染在進行，在這個階段應當詳細追查身體可能的感染源，予以徹底治療。第二階段為全身性發炎反應及心臟瓣膜嚴重破壞後所產生的心臟功能失衡現象，病人有貧血、全身關結酸痛、肌肉酸痛、心臟功能衰退而產生運動耐受性不良及呼吸急促現象，整個過程可以緩慢進行達數個月之久，甚至被當作不明熱（Fever of unknown origin）治療，這個階段如果可以仔細訊問病史，小心進行理學檢查，可以發現引起心內膜炎的原因（如本案例病人有接受牙科治療），及心臟有心雜音的表現。第三階段，病程已經進入嚴重期，所有各器官系統都因為細菌性血栓瀰漫散布，而引起多重器官衰竭，如本案例之心臟衰竭、腎臟衰竭、及腦栓塞等。病人此時接受外科手術，也是在不得已的情形下進行。 感染性心內膜炎，主要診斷依據Modified Duke criteria，分成(1)主要診斷：有血液培養兩套出病原菌，及新發生瓣膜閉鎖不全或心臟超音波可見病兆。(2)次要診斷：有引起此疾病之危險因子、發燒、血栓栓塞在全身之變化，免疫反應，及其它微生物學發現等（Reference：NEJM 2001; 345:1318-1330）。感染性心內膜炎一般培養出來的病原菌，可能是Streptococcus sp. Staphylococcus aureus ，Gram-negative bacilli，或者Fungi，可以隨著是native-valve，或prosthetic-valve及不同年齡，術後發生時間而有不同比例的分佈。 感染性心內膜炎的治療，包含內科抗生素及外科手術，抗生素治療以培養出來結果所作之藥物敏感性試驗為依據，對於有作血液培養卻沒有長出微生物者，就必須依據病人危險因子及臨床表現，給予經驗性用藥，可能要包含penicillin, ampicillin, ceftriaxone或vancomycin通常要合併使用aminoglycoside。手術的時機有(1)心臟衰竭；(2)瓣膜周圍有侵犯；(3)臨床感染無法用抗生素控制下來；或者(4)特別病原菌如Pseudomonas aeruginosa, Brucella sp. Coxiella burnetii, candide sp.等。若病人近期有心內膜炎引起之神經學症狀，一般建議要延遲手術2∼3週，經抗生素充分治療後才進行手術。 繼續教育考題 1. (C) 案例中病人感染性心內膜炎初期的表現不包括下列何者？ A 發燒　 B 脾臟梗塞（spleen infarction） C 心臟衰竭 D 白血球數偏高 2. (B) 脾臟梗塞原因之鑑別診斷包括下列何者？ (1)心臟衰竭 (2)淋巴瘤 (3)感染性心內膜炎 (4)鐮刀型貧血 A (1)(2)(3) B (2)(3)(4) C (1)(2)(4) D (1)(3)(4) 3. (B) 案例中，病人感染性心內膜炎持續進行中，其臨床表現及檢驗結果不包括下列何者？ A 貧血　 B 暈眩　 C 關結酸痛　 D 呼吸急促 4. (A) 案例中，病人發生感染性心內膜炎之原因為何？ A 牙科治療　 B 靜脈注射 C 人工瓣膜置換術後　 D 瓣膜性心臟病 5. (D) 感染性心內膜炎診斷的標準依據何者？ A Modified Child criteria B Ranson criteria C DeBakey criteria D Modified Duke criteria 6. (C) 承上題，診斷標準主診斷為何？ (1)發燒 (2)敗血性血栓栓塞 (3)血液培養不同時間兩套均長出病原菌 (4)新發生瓣膜閉鎖不全 A (1)(2) B (1)(3) C (3)(4) D (2)(4) 7. (C) 有關感染性心內膜炎之敘述，下列何者為非？ A 感染性心內膜炎，病程可達數個月之久 B 感染性心內膜炎，病人初期症狀可以沒有心臟系統方面明顯異常表現 C 感染性心內膜炎，若血液培養沒有長病原菌，即可排除此診斷 D 感染性心內膜炎，有時被當作不明熱治療 8. (A) 感染性心內膜炎其常見病原菌下列何者為非？ A Legionella sp. B Streptococcus sp. C Staphylococcus aureus D Fungi 9. (A) 感染性心內膜炎，須合併外科治療之情形下列何者為非？ A 經過抗生素治療達4週才可　 B 心臟衰竭 C 有瓣膜周圍組織侵犯　 D 臨床感染無法用抗生素控制下來 10. (C) 有關感染性心內膜炎，下列敘述何者為非？ A 感染性心內膜炎，血液培養可能無法長出病原菌 B 有腦部敗血性栓塞時，最好經抗生素治療2-3週，再進行必要外科手術 C 發燒是Modified Duke criteria之主要診斷 D 抗生素治療以培養出的病原菌，依其藥物敏感試驗結果作調整 答案解說 (C ) 詳見病案分析 (B ) 脾臟梗塞原因可分為(1)血液疾病如淋巴瘤、鐮刀型貧血；(2)血栓梗塞如感染性心內膜炎；(3)肉芽瘤。 (B ) 詳見病案分析 (A ) 心內膜炎之危險因子，病人可能有心臟瓣膜上的問題，如二尖瓣脫垂，風濕性心臟病等。原因可能是經過手術產生暫時菌血症，或藥物成癮者使用不潔針頭。本案例病人是經牙科治療中產生暫時菌血症所引起。 (D ) 詳見病案分析，及參考資料NEJM, 2001; 345: 1318-1330。為Modified Duke criteria，有分成主診斷及次要診斷。 (C ) Modified Duke criteria主診斷為：血液培養兩套長出病原菌，及新發生瓣膜閉膜不全或心臟超音波可見病兆。 (C ) 感染性心內膜炎，血液培養可能沒有結果，這時必須考慮一些特殊病原菌，如Bartonella sp., Q fever, Chlamydia sp., HACEK organisms, Legionella sp., Brucella sp.，而給予經驗性用藥。 (A ) 感染性心內膜炎，常見病原菌不包括Legionella sp. (A ) 合併外科治療，最好情況是經過充分抗生素治療，但是若有心臟衰竭，瓣膜周圍組織侵犯，或抗生素無法控制之感染，均須安排手術治療。 (C ) 感染性心內膜炎，若腦部有敗血性血栓，一般建議是經過抗生素治療2∼3週再進行手術，病人術後比較不會產生嚴重神經學併發症。