Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Antimicrob Chemother. 2023 Dec 1;78(12):2902-2908. doi: 10.1093/jac/dkad328.
In critically ill patients with extracorporeal membrane oxygenation (ECMO) attainment of target concentration of isavuconazole is delayed using the routine loading dose.
We investigated the influence of increasing the first loading dose of isavuconazole on plasma concentrations in critically ill patients treated with ECMO.
Fifteen patients were included in this study, and isavuconazole concentrations were measured at several timepoints starting 2 h after the first isavuconazole dose up to 168 h. By interim analysis of isavuconazole concentrations and meticulous screening for adverse events, the first loading dose was stepwise increased from 200 to 300 mg, and finally to 400 mg.
Seven of 15 patients (47%) received standard isavuconazole loading dosage with 200 mg as the first dose, 3/15 (20%) received 300 mg, and 5/15 (33%) received 400 mg isavuconazole as the first dose, followed by subsequent standard dosing in all patients. In patients receiving 400 mg as the first dose all isavuconazole concentrations were significantly higher at timepoints up to the first 24 h, resulting in higher proportions of isavuconazole concentrations ≥1 mg/L compared with patients with other loading dosages. In timepoints ≥24 h after isavuconazole initiation all patient groups reached comparable plasma concentrations, regardless of the first loading dose regimen. We did not observe concentrations above ≥5 mg/L or any adverse events related to isavuconazole administration.
In critically ill patients with ECMO the 400 mg loading dose of isavuconazole resulted in immediate median isavuconazole plasma concentrations ≥1 mg/L and remained constant above this threshold after the first loading dose.
在接受体外膜氧合（ECMO）治疗的危重症患者中，使用常规负荷剂量会导致伊曲康唑的目标浓度达到时间延迟。
我们研究了增加伊曲康唑首剂负荷剂量对接受 ECMO 治疗的危重症患者血浆浓度的影响。
本研究纳入了 15 名患者，在首剂伊曲康唑给药后 2 小时至 168 小时的多个时间点测量伊曲康唑浓度。通过伊曲康唑浓度的中期分析和对不良事件的仔细筛查，首剂负荷剂量逐步从 200mg 增加到 300mg，最终增加到 400mg。
15 名患者中有 7 名（47%）接受了标准的伊曲康唑负荷剂量，首剂为 200mg，3/15（20%）接受了 300mg，5/15（33%）接受了 400mg伊曲康唑作为首剂，随后所有患者均接受标准剂量。在首剂给予 400mg 的患者中，直至首次 24 小时的所有时间点伊曲康唑浓度均显著升高，与给予其他负荷剂量的患者相比，伊曲康唑浓度≥1mg/L 的比例更高。在伊曲康唑起始后≥24 小时的时间点，所有患者组均达到了可比的血浆浓度，而与首剂负荷剂量方案无关。我们未观察到浓度高于≥5mg/L 或与伊曲康唑给药相关的任何不良事件。
在接受 ECMO 的危重症患者中，伊曲康唑的 400mg 负荷剂量可立即使伊曲康唑的中位数血浆浓度≥1mg/L，并且在首剂负荷剂量后保持在该阈值以上。
