Cruciani Mario, Mengoli Carlo, Malena Marina, Bosco Oliviero, Serpelloni Giovanni, Grossi Paolo
Center of Preventive Medicine, HIV Outpatient Clinic, Verona, Italy.
Liver Transpl. 2006 May;12(5):850-8. doi: 10.1002/lt.20690.
We performed a meta-analysis to determine whether antifungal prophylaxis decreases infectious morbidity and mortality in liver transplant patients. We searched for randomized trials dealing with prophylaxis with systemic antifungal agents. We used a fixed effect model, with risk ratio (RR) and 95% confidence interval (CI); we assessed study quality for heterogeneity and publication bias. Six studies (5 double-blind), for a total of 698 patients, compared fluconazole, itraconazole, or liposomal amphotericin to placebo (5 studies) or oral nystatin. Prophylaxis reduced colonization (RR, 0.45; CI, 0.37-0.55), total proven fungal infections (RR, 0.31; CI, 0.21-0.46), which included both superficial (RR, 0.27; CI, 0.16-0.45) and invasive (RR, 0.33; CI, 0.18-0.59) infections, and mortality attributable to fungal infection (RR, 0.30; CI, 0.12-0.75). Prophylaxis did not affect overall mortality (RR, 1.06; CI, 0.69-1.64) or empiric treatment for suspected fungal infection (RR, 0.80; CI, 0.39-1.67). The beneficial effect of antifungal prophylaxis was predominantly associated with the reduction of Candida albicans infection and mortality attributable to C. albicans. Compared to controls, however, patients receiving prophylaxis experienced a higher proportion of episodes of non-albicans Candida, and in particular of C. glabrata. No beneficial effect on invasive Aspergillus infection was observed. In conclusion, our analysis shows a clear, though limited, beneficial effect of antifungal prophylaxis in liver transplant patients. Concerns about the selection of triazole-resistant Candida strains, however, are realistic, and the potential disadvantages of prophylaxis should be weighed against the established benefits.
我们进行了一项荟萃分析，以确定抗真菌预防措施是否能降低肝移植患者的感染发病率和死亡率。我们检索了关于全身性抗真菌药物预防的随机试验。我们使用固定效应模型，计算风险比（RR）和95%置信区间（CI）；我们评估了研究质量的异质性和发表偏倚。六项研究（5项双盲研究），共698例患者，比较了氟康唑、伊曲康唑或脂质体两性霉素与安慰剂（5项研究）或口服制霉菌素。预防措施减少了定植（RR，0.45；CI，0.37 - 0.55）、确诊的真菌总感染（RR，0.31；CI，0.21 - 0.46），其中包括浅表感染（RR，0.27；CI，0.16 - 0.45）和侵袭性感染（RR，0.33；CI，0.18 - 0.59），以及真菌感染导致的死亡率（RR，0.30；CI，0.12 - 0.75）。预防措施未影响总体死亡率（RR，1.06；CI，0.69 - 1.64）或对疑似真菌感染的经验性治疗（RR，0.80；CI，0.39 - 1.67）。抗真菌预防的有益效果主要与白色念珠菌感染的减少以及白色念珠菌导致的死亡率降低有关。然而，与对照组相比，接受预防的患者非白色念珠菌感染，尤其是光滑念珠菌感染的发生率更高。未观察到对侵袭性曲霉感染有有益效果。总之，我们的分析表明抗真菌预防措施在肝移植患者中具有明显但有限的有益效果。然而，对三唑耐药念珠菌菌株选择的担忧是现实存在的，预防措施的潜在弊端应与已确定的益处进行权衡。
