Tigecycline pharmacokinetics in critically ill patients receiving extracorporeal membrane oxygenation: a prospective multicentre pilot study

Abstract

Abstract Background Tigecycline is frequently used to treat multidrug-resistant infections in critically ill patients. However, its pharmacokinetics in patients receiving extracorporeal membrane oxygenation (ECMO) are poorly defined, raising concerns about the adequacy of standard dosing in this population. Methods This prospective, multicentre pilot study included adult ICU patients receiving venovenous (VV) or venoarterial (VA) ECMO and standard tigecycline dosing. Serial plasma samples were collected at steady state to determine tigecycline concentrations using liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters, including maximum plasma concentration (C max ), trough plasma concentration (C min ), area under the concentration–time curve (AUC), and systemic clearance (CL), were calculated. Microbiological samples were obtained before therapy initiation. Pharmacokinetic parameters were compared between ECMO configurations and correlations with organ function markers were assessed using Spearman analysis. Results Fifteen patients were included (13 VV-ECMO, 2 VA-ECMO). Marked interindividual variability in tigecycline exposure was observed. Median C max was 0.50 µg/mL, with consistently low trough concentrations. Plasma levels generally exceeded EUCAST MIC breakpoints for Gram-positive pathogens but were lower for Gram-negative organisms. Patients receiving VA-ECMO exhibited numerically higher tigecycline exposure than those on VV-ECMO. Moderate, non-significant positive correlations were observed between total bilirubin levels and tigecycline exposure. Conclusion Tigecycline pharmacokinetics in ECMO-supported critically ill patients show high variability, with higher exposure in VA-ECMO than in VV-ECMO. Standard dosing may be insufficient, supporting therapeutic drug monitoring and further studies to inform individualized dosing strategies in this complex population.