Ledoux Marie-Pierre, Toussaint Elise, Denis Julie, Herbrecht Raoul
Department of Oncology and Haematology, Hôpital de Hautepierre and Université de Strasbourg, Strasbourg, France.
Laboratoire de Parasitologie et de Mycologie Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
J Antimicrob Chemother. 2017 Mar 1;72(suppl_1):i48-i58. doi: 10.1093/jac/dkx033.
Recently, several randomized studies have been published that will shape treatment decisions in the prevention and management of invasive mould infections. Liposomal amphotericin B is an option for empirical or targeted treatment of invasive aspergillosis or mucormycosis, but for prophylaxis therapy, the triazole class now predominates. The triazole voriconazole is currently regarded as a drug of choice for the treatment of proven or probable invasive aspergillosis, and has shown significantly higher response rates than amphotericin B deoxycholate in this setting, with fewer severe drug-related adverse events. Isavuconazole, the newest triazole agent, offers the advantages of once-daily dosing, a wider spectrum of antifungal activity than voriconazole, predictable pharmacokinetics and fewer CYP enzyme-mediated drug interactions. A recent large randomized clinical trial showed mortality to be similar under isavuconazole or voriconazole in patients with invasive mould disease, with fewer drug-related adverse events in isavuconazole-treated patients. Another study has indicated that isavuconazole is also effective in mucormycosis infections but patient numbers were small and confirmation is awaited. Experimental studies combining different drug classes with antimould activity have been promising, but the clinical database is limited. A large randomized trial of combination therapy compared voriconazole plus the echinocandin anidulafungin versus voriconazole monotherapy in patients with invasive aspergillosis. Results showed the overall response rate to be similar, but combination therapy improved survival for the subpopulation of patients in whom the diagnosis was confirmed by serum and/or bronchoalveolar lavage fluid galactomannan positivity. This active field of research is likely to continue evolving rapidly in the coming years.
最近，有几项随机研究发表，这些研究将对侵袭性霉菌感染的预防和管理中的治疗决策产生影响。脂质体两性霉素B是侵袭性曲霉病或毛霉病经验性或靶向治疗的一种选择，但在预防治疗方面，三唑类药物目前占主导地位。三唑类伏立康唑目前被认为是治疗确诊或疑似侵袭性曲霉病的首选药物，在这种情况下，其显示出比脱氧胆酸盐两性霉素B显著更高的缓解率，且严重药物相关不良事件更少。最新的三唑类药物艾沙康唑具有每日一次给药的优势，抗真菌活性谱比伏立康唑更广，药代动力学可预测且CYP酶介导的药物相互作用更少。最近一项大型随机临床试验表明，侵袭性霉菌病患者使用艾沙康唑或伏立康唑治疗的死亡率相似，但接受艾沙康唑治疗的患者药物相关不良事件更少。另一项研究表明，艾沙康唑在毛霉病感染中也有效，但患者数量较少，有待进一步证实。将不同抗霉菌活性药物类别联合使用的实验研究前景良好，但临床数据库有限。一项联合治疗的大型随机试验比较了伏立康唑加棘白菌素类药物阿尼芬净与伏立康唑单药治疗侵袭性曲霉病患者的疗效。结果显示总体缓解率相似，但联合治疗提高了血清和/或支气管肺泡灌洗液体半乳甘露聚糖阳性确诊患者亚组的生存率。在未来几年，这个活跃的研究领域可能会继续迅速发展。
