Singh N, Gayowski T, Marino I R
Infectious Diseases Section, VA Medical Center, Pittsburgh, PA 15240, USA.
Transpl Int. 1998;11(1):63-5. doi: 10.1007/s001470050104.
Amphotericin B, with or without 5-flucytosine, is currently the therapy of choice for cryptococcal infections. However, amphotericin B, is nephrotoxic and requires long-term venous access for parenteral administration. The combination of fluconazole and flucytosine is synergistic in vitro against Cryptococcus. To date, however, the efficacy of fluconazole and flucytosine for cryptococcosis in liver transplant recipients has never been reported. We report a 66-year-old liver transplant recipient with disseminated invasive cryptococcus (presenting as cryptococcal subcutaneous abscess, osteomyelitis, and serum cryptococcal antigen titer of 1:32). The administration of amphotericin B for 3 weeks led to nephrotoxicity without any clinical response (persistent abscess without change in serum cryptococcal antigen titer). Fluconazole, at a dosage equivalent to 800 mg/day administered orally, and flucytosine, also given orally, led to a clinical response and a steady decline in serum cryptococcal antigen titer, which became negative at 6 weeks of therapy. The patient remains well 18 months after therapy. No adverse effects have been attributed to fluconazole or flucytosine. This combination obviates the nephrotoxicity and the need for parenteral access required for amphotericin B infusion, and it can be administered orally. The combination of fluconazole and flucytosine warrants future controlled trials for the treatment of cryptococcal infection in liver transplant recipients.
两性霉素B,无论是否联合5-氟胞嘧啶,目前都是治疗隐球菌感染的首选疗法。然而,两性霉素B具有肾毒性,并且肠胃外给药需要长期静脉通路。氟康唑和氟胞嘧啶联合使用在体外对隐球菌具有协同作用。然而,迄今为止,氟康唑和氟胞嘧啶用于肝移植受者隐球菌病的疗效尚未见报道。我们报告了一名66岁的肝移植受者,患有播散性侵袭性隐球菌病(表现为隐球菌皮下脓肿、骨髓炎,血清隐球菌抗原滴度为1:32)。给予两性霉素B治疗3周导致肾毒性,且无任何临床反应(脓肿持续存在,血清隐球菌抗原滴度无变化)。口服相当于800毫克/天剂量的氟康唑以及同样口服的氟胞嘧啶,产生了临床反应,血清隐球菌抗原滴度稳步下降,在治疗6周时变为阴性。治疗后18个月患者情况良好。未发现氟康唑或氟胞嘧啶有不良反应。这种联合用药避免了两性霉素B输注所需的肾毒性和肠胃外给药需求,并且可以口服。氟康唑和氟胞嘧啶联合用药值得未来进行治疗肝移植受者隐球菌感染的对照试验。