Antifungal concentrations in mechanically ventilated COVID-19 patients with or without ECMO: The CAPADOSE observational retrospective multicenter Study

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PURPOSE: COVID-19-associated pulmonary aspergillosis (CAPA) is a major co-infection in critically ill patients and is linked to increased mortality. Critical illness and ECMO may affect antifungal pharmacokinetics, raising concerns about drug efficacy. METHODS: This multicenter retrospective study included CAPA patients requiring mechanical ventilation in 20 intensive care units (ICUs) (March 2020 to November 2021), provided at least one antifungal blood level was available. The primary objective was to evaluate whether ECMO influenced the risk of subtherapeutic voriconazole levels. Secondary objectives included analyzing other antifungals and identifying risk factors for underdosing. RESULTS: Among 166 patients, 81 were on ECMO. A total of 358 voriconazole trough concentrations were collected in 150 patients. Subtherapeutic levels (<2 mg/L) were observed in 58 patients (39%) at first sampling and in 84 patients (56%) during the ICU stay, with no difference between ECMO and non-ECMO groups. No correlation was found between ECMO membrane duration and voriconazole levels. Daily dose was associated with low levels in univariate analysis only. Among 26 patients treated with isavuconazole, 11 (42%) had initial subtherapeutic levels. Renal replacement therapy, not ECMO, was associated with low isavuconazole levels (odds ratios = 7.5, P = 0.029). CONCLUSION: Over half of CAPA patients had subtherapeutic antifungal levels, but ECMO did not significantly influence drug exposure.

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