Winston D J, Pakrasi A, Busuttil R W
Department of Medicine, University of California, Los Angeles, Medical Center, 90095, USA.
Ann Intern Med. 1999 Nov 16;131(10):729-37. doi: 10.7326/0003-4819-131-10-199911160-00003.
Among persons who receive solid organ transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective.
To evaluate the efficacy and safety of prophylactic fluconazole in liver transplant recipients.
Randomized, double-blind, placebo-controlled trial.
University-affiliated transplantation center.
212 liver transplant recipients who received fluconazole (400 mg/d) or placebo until 10 weeks after transplantation.
Fungal colonization, proven superficial or invasive fungal infection, drug-related side effects, and death.
Fungal colonization increased in patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003).
Prophylactic fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.
在接受实体器官移植的患者中，肝移植受者发生侵袭性真菌感染的发生率最高；然而，尚无抗真菌预防措施被证明有效。
评估预防性使用氟康唑对肝移植受者的疗效和安全性。
随机、双盲、安慰剂对照试验。
大学附属医院移植中心。
212例肝移植受者，接受氟康唑（400mg/d）或安慰剂治疗直至移植后10周。
真菌定植、确诊的浅表或侵袭性真菌感染、药物相关副作用及死亡情况。
接受安慰剂的患者真菌定植增加（从60%增至90%），而接受氟康唑的患者真菌定植减少（从70%降至28%）。104例接受安慰剂的患者中有45例（43%）发生确诊的真菌感染，而108例接受氟康唑的患者中仅有10例（9%）发生（P<0.001）。氟康唑预防了浅表感染（104例接受安慰剂的患者中有29例[28%]发生感染，而108例接受氟康唑的患者中有4例[4%]发生感染；P<0.001）和侵袭性感染（104例接受安慰剂的患者中有24例[23%]发生感染，而108例接受氟康唑的患者中有6例[6%]发生感染；P<0.001）。氟康唑预防了大多数念珠菌属引起的感染，但光滑念珠菌除外。然而，对氟康唑固有耐药的微生物引起的感染和定植似乎并未增加。氟康唑与任何肝毒性均无关联。接受氟康唑的患者血清环孢素水平较高，且有更多的不良神经事件（13例接受氟康唑的患者出现头痛、震颤或癫痫发作，而接受安慰剂的患者有3例；P=0.01）。尽管两组的总死亡率相似（氟康唑组108例中有12例[11%]，安慰剂组104例中有15例[14%]；P>0.2），但氟康唑组与侵袭性真菌感染相关的死亡人数少于安慰剂组（108例患者中有2例[2%]）（104例患者中有13例[13%]）（P=0.003）。
肝移植后预防性使用氟康唑可减少真菌定植，预防浅表和侵袭性真菌感染，且无明显肝毒性。尽管预防性使用氟康唑可减少真菌感染导致的死亡，但并未改善总体生存率。接受预防性氟康唑治疗的患者需要密切监测血清环孢素水平以避免神经毒性。
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