Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum Nürnberg, Paracelsus Medical University, Nuremberg, Germany.
Institute for Biomedical and Pharmaceutical Research, Nuremberg-Heroldsberg, Germany.
Mycoses. 2022 Jul;65(7):747-752. doi: 10.1111/myc.13469. Epub 2022 May 31.
The broad-spectrum triazole isavuconazole is used for the treatment of invasive aspergillosis and mucormycosis. Data regarding human plasma concentrations in clinical routine of the drug are rare.
Plasma concentrations of isavuconazole were determined in critically ill ICU patients while considering different patients' characteristics.
Retrospective analysis of isavuconazole plasma concentrations were obtained as part of routine therapeutic drug monitoring (TDM) of ICU patients with invasive aspergillosis or other fungal infections treated with isavuconazole. Plasma levels 0-4 h after last dosing were defined as peak levels (C ), those 20-28 h after last dosing as trough levels (C ).
Overall, 223 isavuconazole levels of 41 patients were analysed, divided into 141 peak levels and 82 trough levels. The overall median C was 2.36 μg/ml (mean 2.43 μg/ml, range 0.41-7.79 μg/ml) and the overall median C was 1.74 μg/ml (mean 1.77 μg/ml, range 0.24-4.96 μg/ml). In total, 31.7% of the C values of the total cohort were below the plasma target concentrations of 1 μg/ml, defined as EUCAST antifungal clinical breakpoint for Aspergillus fumigatus. Both peak and trough plasma levels of isavuconazole were significantly lower among patients with a body mass index (BMI) ≥25. In addition, a significant correlation was observed between isavuconazole trough levels and sepsis-related organ failure assessment (SOFA) score.
This study shows that isavuconazole plasma concentrations vary in critical ill ICU patients. Significantly lower isavuconazole levels were associated with elevated BMI and higher SOFA score indicating a need of isavuconazole TDM in this specific patient population.
广谱三唑伊曲康唑用于治疗侵袭性曲霉病和毛霉病。关于该药在临床常规中人体血浆浓度的数据很少。
在考虑不同患者特征的情况下，测定重症监护病房（ICU）危重症患者的伊曲康唑血浆浓度。
对接受伊曲康唑治疗侵袭性曲霉病或其他真菌感染的 ICU 患者进行常规治疗药物监测（TDM）的部分伊曲康唑血浆浓度进行回顾性分析。最后一次给药后 0-4 小时的血浆水平定义为峰浓度（C ），最后一次给药后 20-28 小时的血浆水平定义为谷浓度（C ）。
共分析了 41 名患者的 223 个伊曲康唑水平，分为 141 个峰浓度和 82 个谷浓度。总体中位数 C 为 2.36μg/ml（平均 2.43μg/ml，范围 0.41-7.79μg/ml），总体中位数 C 为 1.74μg/ml（平均 1.77μg/ml，范围 0.24-4.96μg/ml）。在总队列中，有 31.7%的 C 值低于 1μg/ml 的血浆靶浓度，这被定义为 EUCAST 抗真菌临床折点，适用于烟曲霉。伊曲康唑的峰浓度和谷浓度均显著低于 BMI≥25 的患者。此外，伊曲康唑谷浓度与脓毒症相关器官衰竭评估（SOFA）评分之间存在显著相关性。
本研究表明，伊曲康唑在重症监护病房（ICU）危重症患者中的血浆浓度存在差异。BMI 升高和 SOFA 评分较高与伊曲康唑水平降低显著相关，表明该特定患者人群需要进行伊曲康唑 TDM。
