Case Discussion      A 49-year-old woman had been diagnosed as having diabetes mellitus for 15 years and end-stage renal disease for 2 years. She started to undergo intermittent hemodialysis for the first 6 months, which was subsequently switched to peritoneal dialysis (PD) after receipt of adequate education and training for PD. She ever suffered from several episodes of bacterial peritonitis for which she received courses of complete antibiotic therapy without complication. The day before she came back to the monthly PD clinic, she experienced a low-grade fever and mild abdominal pain. The effluent became cloudy, although the catheter exit site was clean without erythematous skin change or discharge. The results of laboratory tests on the day of PD clinic were also suggestive of peritonitis (please see the laboratory result), and vancomycin and a third-generation cephalosporin were begun empirically. A few days later, she was free of symptoms and the effluent became clear. However, a new fever and abdominal pain developed and the effluent became cloudy two weeks after she completed the previous course of antibiotic treatment. The results of laboratory tests were suggestive of recurrent peritonitis; dialysate effluent contained 150 white blood cells/mm3 and 70% of the white blood cells were polymorphonuclear neutrophils. Despite therapy with vancomycin and a third-generation cephalosporin, high fever, abdominal pain and presence of cloudy effluent persisted. Meanwhile, the oral hypoglycemic agents failed to effectively control her blood glucose at the usually prescribed doses. She also exhibited chills, tachycardia and peripheral coldness. Under the impression of uncontrolled PD-related peritonitis and sepsis, she was admitted for further management. < Laboratory and Image Study > 1. CBC and differential count Day after admission WBC K/μL Hgb g/dL Hct % Plt K/μL Band % Seg % Eos % Lym % PD clinic 9.98 10.3 30.5 460 0 88 0.2 2.5 Admission day 1 15.54 9.6 28.8 470 0 92 3.6 2.5 Admission day 3 10.98 9.8 29.8 440 0 87 4.0 2.2 Admission day 7 9.03 10.1 30.7 460 0 82 2.0 2.3 2. Biochemistry   Day after admission BUN mg/dl Cre mg/dl Na mmol/l K mmol/l GOT U/l PD clinic 75 8.5 141 4.8 29 Admission day 3 77 8.3 138 4.6 30   3. Tests for Dialysate    Day after admission appearance WBC count (/mm3) PMN % Gram stain Bacterial culture Fungus culture PD clinic cloudy 220 70 + MSSA - Admission day 1 cloudy 365 80 yeast-like organism - Candida albicans Admission day 5 mildly cloudy 150 69 - - - Admission day 7 clear 101 55 - - - Note: MSSA: methicillin-resistant Staphylococcus aureus 4. Blood culture Admission day 1: bacterial: negative; C. albicans: positive 5. CXR: mildly enlarged heart size and clear lung fields < Course and Treatment >      On admission, she was empirically treated with intraperitoneal and intravenous vancomycin and a third-generation cephalosporin. Fluconazole 200 mg was administered by intraperitoneal as well as intravenous route. After the culture results were available that grew C. albicans, anti-bacterial agents were discontinued and fluconazole was continued based on the microbiological susceptibility. PD catheter was removed and she was placed on intermittent hemodialysis. After two weeks of intravenous fluconazole, the patient was afebrile and was discharged with oral fluconazole for two more weeks. < 病例分析 >      Peritoneal dialysis (PD) peritonitis是在PD病人非常常見的併發症。然而大多PD peritonitis 是源自細菌感染，相對而言，黴菌性PD peritonitis 則不常見。當PD病患出現以下三項臨床表現時，必須要懷疑有PD peritonitis: 發燒、腹痛及混濁的透析液。但是發燒、腹痛在成年病患並不是一定會出現，而混濁的透析液則是 PD peritonitis 一定會出現的表現。當懷疑一位病患有PD peritonitis時，除了必要的病史及理學檢查外，還必須要立即採取透析液做Gram stain、cell count 及微生物的培養。當一位PD病患的透析液中發現: >100 white blood cells/mm3 及 > 50% 的 polymorphonuclear neutrophils 時，就確定此病患有PD peritonitis。若是黴菌性PD peritonitis，則偶爾可在透析液中發現 eosinophil 比例升高。有時即使確有PD peritonitis，但Gram stain還是可能呈現陰性，儘管如此 Gram stain 仍然一定要做，因為 Gram stain 不只可以篩檢細菌，還可篩檢是否有黴菌的存在。由於黴菌性PD peritonitis 的高死亡率及須立即拔管，所以 Gram stain 可爭取時效，而不需等待培養報告。因此當懷疑 PD peritonitis 時，Gram stain 是所有病患都必要的檢查。當懷疑 PD peritonitis 時，即使 Gram stain 呈現陰性，但還是要先針對革蘭性陰性及陽性菌給予經驗性抗生素。至於抗黴菌藥物，由於發生率不高，因此並不是 PD peritonitis 的第一線藥物。      黴菌性 PD peritonitis 常發生在病患之前有過抗細菌性抗生素的療程，或本身的疾病使患者易發生黴菌性PD peritonitis，如 diabetes mellitus 等。對於黴菌性 PD peritonitis，由於發生數不如細菌性 PD peritonitis，所以至今並未有大規模的前瞻性研究，文獻多局限於病例報告或回顧性研究，因此經驗不多，而治療以專家經驗為主。根據 International Society for Peritoneal Dialysis’ 2005 Guideline Update，初期治療可以考慮使用腹內注射 amphotericin B 直到得到培養結果，因為 amphotericin B 的腎毒性較大，雖然PD病患已接受透析，但仍需盡量保存殘存腎功能，且會造成疼痛及有產生 chemical peritonitis 的疑慮，因此也有文獻指出優先使用 fluconazole 或 voriconazole，而不建議 amphotericin B。藥物治療同時必須伴隨透析管路的移除。腹內注射及靜脈注射藥物劑量可考慮200 mg，而之後可換成每天口服 flucytosine 1000 mg 及 fluconazole 100至200 mg，共十天。但也有文獻建議至少2至4星期。      在黴菌性 PD peritonitis 的治療除了抗黴菌藥物外，還包括管路的移除才算完整。表一則亦列出其他需移除管路的情況。一旦確認是黴菌性 PD peritonitis 時，就必須要將透析管移除，由於死亡率高達25%，因此並不需為了保存管路而冒險，主要的考量除了高死亡率之外，也在於盡量保存腹膜功能。至於管路移除之後，需隔多久才可再植入新管，目前並無定論。經驗上，在拔除舊管後，至少需等待2至3星期的時間。 Table 1. Indications for Catheter Removal for Peritoneal Dialysis-Related Infections Refractory peritonitis Relapsing peritonitis Refractory exit-site and tunnel infection Fungal peritonitis Consider catheter removal if not responding to therapy Mycobacterial peritonitis Multiple enteric organisms < References > Peritoneal Dialysis International, Vol. 25, pp. 107–131, 2005. Comprehensive Clinical Nephrology 2nd edition 繼續教育考題 1. (C) 1. Peritoneal dialysis (PD) peritonitis的常見初期症狀不包括？ A Abdominal pain B Cloudy effluent C Pus discharge from exit site D Fever 2. (A) 對於 PD peritonitis的診斷何者正確？ A Dialysate contains >100 WBC/mm3 and >50% polymorphonuclear neutrophils B Fever and abdominal pain are always present C Usually results from infection with mixed flora D Need to stop PD immediately to prevent peritoneum injury 3. (B) 有關PD peritonitis的描述，何者錯誤？ A Most of the etiologies are of bacterial origin B Fever is universally present in patients with PD peritonitis C Dialysate contains >100 WBC/mm3 and >50% polymorphonuclear neutrophils D Catheter can usually be preserved 4. (C) PD相關的fungal peritonitis的描述，何者正確？ A Fungal peritonitis is more common than bacterial peritonitis B PD catheter can usually be preserved C Most fungal peritonitis is associated with Candida species D Fungal peritonitis is associated with previous repeated anti-fungal treatment 5. (D) 何時不需立即考慮移除PD catheter？ A Mycobacterial peritonitis B Fungal peritonitis C Relapsing peritonitis D Pseudomonas peritonitis 6. (C) 對於PD peritonitis的相關治療方式，何者不正確？ A Antibiotics for both Gram-positive and Gram-negative bacteria are the first-line therapeutic agents B Anti-fungal agents are not the first-line therapeutic agents C Amphotericin B administered intraperitoneally is the only agent available for treatment of fungal peritonitis D Catheter should be removed in patients with fungal peritonitis 答案解說 (C) 當PD病患出現以下三項臨床表現時，必須要懷疑有PD peritonitis: 發燒、腹痛及混濁的透析液。但是發燒、腹痛在成年病患並不是一定會出現，而混濁的透析液則是 PD peritonitis 一定會出現的表現。Exit site 的pus 較像是出口處的感染，雖然exit site 感染可能導致peritonitis，但peritonitis 較少以此表現。 (A )  PD peritonitis的症狀及徵像: 發燒、腹痛及混濁的透析液。當懷疑一位病患有PD peritonitis時，除了必要的病史及理學檢查外，還必須要立即採取透析液做Gram stain、cell count 及微生物的培養。當一位PD病患的透析液中發現: > 100 white blood cells/mm3 及 > 50% 的 polymorphonuclear neutrophils 時，就確定此病患有PD peritonitis。若是黴菌性PD peritonitis，則偶爾可在透析液中發現 eosinophil 比例升高。PD peritonitis 通常是單一菌種造成。一般PD peritonitis時並不需暫停PD。 (B ) 大多PD peritonitis 是源自細菌感染，而且管路可被保留。 混濁的透析液則是 PD peritonitis 一定會出現的表現。PD病患的透析液中發現: >100 white blood cells/mm3 及 >50% 的 polymorphonuclear neutrophils 時，就確定此病患有PD peritonitis。  (C) 大多PD peritonitis 是源自細菌感染，相對而言，黴菌性PD peritonitis 則不常見。在黴菌性 PD peritonitis 的治療除了抗黴菌藥物外，還包括管路的移除才算完整。黴菌性 PD peritonitis 常發生在病患之前有過抗細菌性抗生素的療程，或本身的疾病使患者易發生黴菌性PD peritonitis，如 diabetes等。而病源體以Candida為主。 (D) 根據表一，Pseudomonas aeruginosa peritonitis 並不是管路的移除的絕對適應症，然而若一直出現重複性 Pseudomonas peritonitis 感染或對治療無效時，仍須考慮拔管。 (C) 由於大多PD peritonitis 是源自細菌感染， 因此抗黴菌藥物，並不是 PD peritonitis 的第一線藥物。而也還有其他藥物如fluconazole等可使用。此外，在黴菌性PD peritionitis時，管路是一定移除。