Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID‐19

Abstract

BackgroundThe broad‐spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis.ObjectivesIsavuconazole plasma concentrations in critically ill ICU patients with or without COVID‐19 and invasive fungal infection were determined, and factors for sub‐therapeutic drug levels (<1 μg/mL) were evaluated.Patients and MethodsIsavuconazole plasma levels were measured as part of therapeutic drug monitoring (TDM) in ICUs of a tertiary hospital. Concentrations determined 20–28 h after previous dosing were defined as trough (Cmin) levels. A total of 160 Cmin levels from 62 patients with invasive fungal infections were analysed, 30 of which suffering from COVID‐19. Patient characteristics included into univariable and multivariable analyses were gender, age, COVID‐19 status, body mass index (BMI), sepsis‐related organ failure (SOFA) score, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) requirement.ResultsThe mean Cmin of isavuconazole in all patients was 1.64 μg/mL (interquartile range 0.83–2.24 μg/mL, total range 0.24–5.67 μg/mL). In total, 34.4% of the Cmin values (corresponding to 46.8% of patients) were below a threshold concentration of 1 μg/mL. Drug concentrations between patients with or without COVID‐19 did not differ (p = .43). In contrast, levels were significantly lower in patients with female sex (p = .0007), age ≤ 65 years (p = .002), BMI > 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001).ConclusionsIsavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed.

Antifungals in Patients With Extracorporeal Membrane Oxygenation: Clinical Implications

“…In 2 recently published cases, the 24-hour areas under the concentration–time curve and trough concentrations of isavuconazole were lower in both patients with ECMO in comparison with previously published data from non-ECMO patients [ 26 ]. Another case series including 9 critically ill patients with IFD and ECMO revealed that isavuconazole plasma levels were lower in patients receiving ECMO therapy compared with patients without ECMO [ 27 ]. A recent study included 18 critically ill patients, of whom 5 had CAPA, ECMO, and isavuconazole treatment.…”