Tonin Fernanda S, Steimbach Laiza M, Borba Helena H, Sanches Andreia C, Wiens Astrid, Pontarolo Roberto, Fernandez-Llimos Fernando
Pharmaceutical Sciences Postgraduate Program, Universidade Federal do Paraná, Curitiba, Brazil.
Department of Pharmacy, Universidade Estadual do Oeste do Paraná, Cascavel, Brazil.
J Pharm Pharmacol. 2017 Dec;69(12):1672-1683. doi: 10.1111/jphp.12802. Epub 2017 Aug 17.
Despite its broad spectrum, conventional amphotericin B (AB) is associated with serious adverse events. Lipid-based formulations may offer safer options. We aimed to synthesize the evidence of efficacy and safety of AB formulations.
We performed a systematic review and network meta-analysis (NMA) to compare all available formulations: conventional AB; lipid complex or ABLC; colloidal dispersion or ABCD; liposomal or LAB; AB in Intralipid. Randomized controlled trials were searched in four databases. Cure, fever, chills, nephrotoxicity, death and drug discontinuation were assessed. NMA was based on Bayesian methods accounting for direct and indirect comparisons. Probability ranks estimating the best formulation were built for each outcome. The relative benefit-risk of formulations was assessed with stochastic multicriteria acceptability analyses (SMAA).
We identified 25 trials (n = 2996). No significant differences among drugs were observed for cure or death. All lipid-based formulations were safer than conventional AB for nephrotoxicity. AB-Intralipid was more tolerable than conventional AB and caused less chills than ABCD. AB-Intralipid was the best therapy (>60%) regarding nephrotoxicity, fever, chills and discontinuation. The scenario from SMAA favoured AB-Intralipid (81% acceptability). Conventional AB was secondary to all lipid-based formulations.
Amphotericin B-Intralipid was identified as safer, cost-saving treatment in comparison with other formulations.
尽管传统两性霉素B（AB）具有广泛的抗菌谱，但它会引发严重的不良事件。基于脂质的制剂可能提供更安全的选择。我们旨在综合AB制剂疗效和安全性的证据。
我们进行了一项系统评价和网状Meta分析（NMA），以比较所有可用的制剂：传统AB；脂质复合物或ABLC；胶体分散液或ABCD；脂质体或LAB；含脂肪乳剂的AB。在四个数据库中检索随机对照试验。评估治愈率、发热、寒战、肾毒性、死亡率和停药情况。NMA基于贝叶斯方法，考虑直接和间接比较。为每个结局构建估计最佳制剂的概率排名。通过随机多标准可接受性分析（SMAA）评估制剂的相对获益风险。
我们纳入了25项试验（n = 2996）。在治愈率或死亡率方面，未观察到药物之间存在显著差异。所有基于脂质的制剂在肾毒性方面均比传统AB更安全。含脂肪乳剂的AB比传统AB耐受性更好，且寒战比ABCD更少。在肾毒性、发热、寒战和停药方面，含脂肪乳剂的AB是最佳治疗方法（>60%）。SMAA的分析结果支持含脂肪乳剂的AB（可接受性为81%）。传统AB仅次于所有基于脂质的制剂。
与其他制剂相比，含脂肪乳剂的两性霉素B被认为是更安全、更具成本效益的治疗方法。
