Radboudumc-CWZ Center of Expertise for Mycology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
J Antimicrob Chemother. 2024 Aug 1;79(8):1801-1810. doi: 10.1093/jac/dkae139.
Isavuconazole is a relatively new antifungal agent indicated for the management of various invasive fungal diseases (IFDs), including invasive aspergillosis. Information on real-world experience with isavuconazole is scarce. This retrospective observational study aimed to describe the usage of isavuconazole in clinical practice with an in-depth evaluation of individual isavuconazole exposure.
Patients treated with isavuconazole were evaluated based on retrospective data, including therapeutic drug monitoring (TDM) data and efficacy and safety data. Additionally, we calculated the individual isavuconazole exposure described by the average AUC24 over the first 7 days of treatment by means of non-linear mixed-effects modelling and compared this with the currently desired lower target AUC of 60 mg·h/L.
Ninety-nine patients treated with isavuconazole were evaluated. In our real-life cohort, isavuconazole was often deployed off-label in patients with non-classical host factors and infections with non-Aspergillus and non-Mucorales species. Isavuconazole was most often chosen for its safety profile, even after prior triazole treatment with manifestations of toxicity. TDM and subsequent dosage adjustments were frequently performed. The individual average AUC24 over 7 days was above 60 mg·h/L in 29 out of 77 (37.7%) patients.
This overview provides practical insights that can aid clinicians in the management of their patients with IFD. Our study shows that isavuconazole was used in a diverse patient population and was well tolerated overall. Individual isavuconazole exposure reflected by the average AUC24 over the first 7 days of treatment was generally low and variable. Dosage adjustments following TDM were frequently performed. Our experience shows that isavuconazole is a feasible alternative after prior azole treatment.
伊曲康唑是一种新型抗真菌药物，适用于治疗各种侵袭性真菌感染（IFD），包括侵袭性曲霉病。关于伊曲康唑在真实世界中的经验信息很少。本回顾性观察性研究旨在描述伊曲康唑在临床实践中的使用情况，并对个体伊曲康唑暴露情况进行深入评估。
根据回顾性数据评估接受伊曲康唑治疗的患者，包括治疗药物监测（TDM）数据以及疗效和安全性数据。此外，我们通过非线性混合效应模型计算了前 7 天治疗期间平均 AUC24 描述的个体伊曲康唑暴露情况，并将其与目前所需的 60mg·h/L 较低目标 AUC 进行比较。
共评估了 99 例接受伊曲康唑治疗的患者。在我们的真实世界队列中，伊曲康唑常被用于无经典宿主因素的患者和非曲霉和非毛霉属物种感染。伊曲康唑常因其安全性而被选择，即使在先前使用三唑类药物治疗并出现毒性表现后。经常进行 TDM 和随后的剂量调整。在 77 例患者中的 29 例（37.7%）中，前 7 天的个体平均 AUC24 超过 60mg·h/L。
本综述提供了有助于临床医生管理 IFD 患者的实用见解。我们的研究表明，伊曲康唑在多种患者人群中使用，总体上耐受性良好。前 7 天治疗期间平均 AUC24 反映的个体伊曲康唑暴露情况普遍较低且多变。经常进行 TDM 后的剂量调整。我们的经验表明，伊曲康唑是先前唑类药物治疗后的可行替代药物。
