Can linezolid be validly measured in endotracheal aspiration in critically ill patients? A proof-of-concept trial.

Background: Therapeutic drug monitoring (TDM) of anti-infectives such as linezolid is routinely performed in blood of intensive care unit (ICU) patients to optimize target attainment. However, the concentration at the site of infection is considered more important for a successful therapy. Until now, bronchoalveolar lavage (BAL) is the gold standard to measure intrapulmonary concentrations of anti-infective agents. However, it is an invasive method and unsuitable for regular TDM. The aim of this proof-of-concept study was to investigate whether it is possible to reliably determine the intrapulmonary concentration of linezolid from endotracheal aspiration (ENTA).

Methods: Intubated ICU patients receiving 600 mg intravenous linezolid twice daily were examined in steady state. First, preliminary experiments were performed in six patients to investigate which patients are suitable for linezolid measurement in ENTA. In a second step, trough and peak linezolid concentrations of plasma and ENTA were determined in nine suitable patients.

Results: Linezolid can validly be detected in ENTA with viscous texture and > 0.5 mL volume. The mean (SD) linezolid trough concentration was 2.02 (1.27) mg/L in plasma and 1.60 (1.36) mg/L in ENTA, resulting in a median lung penetration rate of 104%. The mean (SD) peak concentration in plasma and ENTA was 10.77 (5.93) and 4.74 (2.66) mg/L.

Conclusions: Linezolid can validly be determined in ENTA with an adequate texture and volume. The penetration rate is comparable to already published BAL concentrations. This method might offer a simple and non-invasive method for TDM at the site of infection "lung". Due to promising results of the feasibility study, comparison of ENTA and BAL in the same patient should be investigated in a further trial.