Winston Drew J, Busuttil Ronald W
Transplantation. 2002 Sep 15;74(5):688-95. doi: 10.1097/00007890-200209150-00017.
Liver transplant recipients at high risk for serious fungal infections frequently receive fluconazole or an amphotericin B preparation for antifungal prophylaxis. Because of concerns about fungal resistance with fluconazole, safety with amphotericin B, and the cost of lipid formulations of amphotericin, alternative prophylactic regimens are needed. In this randomized, controlled trial, we compared the efficacy and safety of oral itraconazole solution with intravenous/oral fluconazole for prevention of fungal infections.
Adult liver transplant recipients were randomized to receive either oral itraconazole solution (200 mg every 12 hr) or intravenous/oral fluconazole (400 mg every 24 hr). Each study drug was started immediately before transplant surgery and continued for 10 weeks after transplantation. Patients were evaluated for fungal colonization, proven invasive or superficial fungal infection, drug-related side effects, and death.
Fungal colonization decreased from baseline to week 8 after transplantation in both the itraconazole patients (67% to 25%, P<0.001) and the fluconazole patients (77% to 30%, P<0.001). Proven fungal infection developed in 9 (9%) of 97 itraconazole patients and in 4 (4%) of 91 fluconazole patients (P =0.25). The number of proven invasive fungal infections (seven with itraconazole [7%], three with fluconazole [3%]) and proven superficial fungal infections (two with itraconazole [2%], one with fluconazole [1%]) were also similar in both groups of patients. Organisms causing infection were (four patients), (three patients), and species (two patients) in the itraconazole group and (two patients), (one patient), and species (one patient) in the fluconazole group. Mortality from fungal infection was very low and occurred in only 1 (0.5%) of 188 patients. Except for more frequent gastrointestinal side effects (nausea, vomiting, diarrhea) with itraconazole, both itraconazole and fluconazole were well tolerated and not associated with any hepatotoxicity. Mean trough plasma concentrations of itraconazole were greater than 250 ng/mL throughout the study and were not affected by H -receptor antagonists or antacids.
Oral itraconazole solution has adequate bioavailability in liver transplant recipients for effective antifungal prophylaxis. Similar to fluconazole, prophylactic oral itraconazole decreases fungal colonization and is associated with a low incidence of serious or fatal fungal infections. Except for gastrointestinal side effects, oral itraconazole solution is well tolerated and has no significant hepatotoxicity.
严重真菌感染高危的肝移植受者常接受氟康唑或两性霉素B制剂进行抗真菌预防。由于担心氟康唑导致真菌耐药、两性霉素B的安全性以及两性霉素脂质制剂的成本，需要替代预防方案。在这项随机对照试验中，我们比较了口服伊曲康唑溶液与静脉/口服氟康唑预防真菌感染的疗效和安全性。
成年肝移植受者被随机分为接受口服伊曲康唑溶液（每12小时200mg）或静脉/口服氟康唑（每24小时400mg）。每种研究药物在移植手术前立即开始使用，并在移植后持续使用10周。对患者进行真菌定植、确诊的侵袭性或浅表真菌感染、药物相关副作用及死亡情况的评估。
伊曲康唑组患者（67%至25%，P<0.001）和氟康唑组患者（77%至30%，P<0.001）从基线至移植后第8周真菌定植均减少。97例伊曲康唑组患者中有9例（9%）发生确诊真菌感染，91例氟康唑组患者中有4例（4%）发生确诊真菌感染（P =0.25）。两组患者确诊的侵袭性真菌感染数量（伊曲康唑组7例[7%]，氟康唑组3例[3%]）和确诊的浅表真菌感染数量（伊曲康唑组2例[2%]，氟康唑组1例[1%]）也相似。伊曲康唑组引起感染的病原体为（4例患者）、（3例患者）和种（2例患者），氟康唑组为（2例患者）、（1例患者）和种（1例患者）。真菌感染导致的死亡率非常低，188例患者中仅1例（0.5%）死亡。除伊曲康唑胃肠道副作用（恶心、呕吐、腹泻）更常见外，伊曲康唑和氟康唑耐受性均良好，且均未出现任何肝毒性。在整个研究过程中，伊曲康唑的平均谷浓度血浆浓度均大于250ng/mL，且不受H受体拮抗剂或抗酸剂的影响。
口服伊曲康唑溶液在肝移植受者中具有足够的生物利用度，可有效进行抗真菌预防。与氟康唑相似，预防性口服伊曲康唑可减少真菌定植，且严重或致命真菌感染的发生率较低。除胃肠道副作用外，口服伊曲康唑溶液耐受性良好，无明显肝毒性。
