BACKGROUND Invasive fungal infections are a major cause of morbidity and mortality. Newer antifungals may provide similar efficacy with improved safety compared to older more established treatments. This study aimed to compare clinically relevant safety and efficacy outcomes in real world patients treated with isavuconazole, voriconazole, or posaconazole. METHODS This single center retrospective matched cohort study evaluated adults between January 2015 and December 2017. The primary outcome was a composite safety analysis of antifungal related QTc prolongation, elevated liver function tests (> 5 times ULN), or any documented adverse drug event. Key secondary outcomes included: individual safety events, 30-day readmissions, magnitude of drug interactions with immunosuppressive therapy, and overall cost. RESULTS A total of 100 patients were included: 34 patients in the voriconazole group and 33 patients within each of the isavuconazole and posaconazole groups. The composite safety outcome occurred in 40% of the total cohort and was different between isavuconazole (24.2%), voriconazole (55.9%), and posaconazole (39.4%; p = 0.028). Change in QTc (p < 0.01) and magnitude of immunosuppression dose reduction (p = 0.029) were different between the three groups. No differences in mortality, length of stay, readmission, or infection recurrence were observed between groups (p > 0.05 for all). The overall medication cost, when including therapeutic drug monitoring, was not different between treatments (p = 0.36). CONCLUSIONS Patients treated with isavuconazole resulted in fewer composite safety outcomes, driven by decreased incidence of QTc prolongation, compared to patients treated with voriconazole or posaconazole. Overall drug cost was not significantly different between the treatment therapy options.

中文翻译：

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在学术医学中心对硫酸异氟康唑鎓，伏立康唑和泊沙康唑进行侵袭性真菌感染管理的比较评估。

背景技术侵袭性真菌感染是发病率和死亡率的主要原因。与较老的较成熟的治疗方法相比，较新的抗真菌剂可提供相似的疗效和更高的安全性。这项研究旨在比较在实际患者中使用伊沙康康唑，伏立康唑或泊沙康唑治疗的临床相关安全性和疗效结果。方法这项单中心回顾性队列研究对2015年1月至2017年12月之间的成年人进行了评估。主要结果是对抗真菌相关QTc延长，肝功能检查升高（ULN的5倍以上）或任何不良药物事件进行了综合安全性分析。主要的次要结果包括：个体安全事件，30天再入院，药物与免疫抑制疗法相互作用的程度以及总费用。结果共纳入100例患者：伏立康唑组34例，伊沙康康和泊沙康唑各33例。综合安全性结果发生在总队列的40％中，伊沙康康唑（24.2％），伏立康唑（55.9％）和泊沙康唑（39.4％； p = 0.028）之间存在差异。三组患者的QTc变化（p <0.01）和免疫抑制剂量降低幅度（p = 0.029）不同。两组之间在死亡率，住院时间，再入院率或感染复发方面均无差异（对于所有患者，p> 0.05）。包括治疗药物监测在内的总药物成本在不同治疗之间没有差异（p = 0.36）。结论接受伊沙康康治疗的患者降低了复合安全性结果，与伏立康唑或泊沙康唑治疗的患者相比，QTc延长的发生率降低是导致这种情况的主要原因。总体药物成本在治疗方案之间没有显着差异。