Serum linezolid concentrations are reduced in critically ill patients with pulmonary infections: A prospective observational study

Rationale: The concentration-time profile of linezolid varies considerably in critically ill patients. Question of interest is, if the site of infection influences linezolid serum concentrations.

Methods: 68 critically ill patients, treated with linezolid, were included. The concentration-time-profile for linezolid was determined using maximum a-posteriori predictions. A trough concentration (C_min) between 2 and 10 mg/L was defined as the target. A generalized linear model (GLM) was established to evaluate potential covariates.

Results: The indications for linezolid therapy were in descending order: peritonitis (38.2%), pneumonia (25.0%), infectious acute respiratory distress syndrome (ARDS) (19.1%), and other non-pulmonary infection (17.7%). 27.2 and 7.9% of C_min were subtherapeutic and toxic, respectively. In the GLM, ARDS (mean: -2.1 mg/L, CI: -3.0 to -1.2 mg/L) and pneumonia (mean: -2.2 mg/L, CI: -2.8 to -1.6 mg/L) were significant (p < 0.001) determinants of C_min. Patients with ARDS (mean: 2.3 mg/L, 51.2% subtherapeutic, 0.0% toxic) and pneumonia (mean: 3.5 mg/L, 41.5% subtherapeutic, 7.7% toxic) had significantly (p < 0.001) lower C_min than those with peritonitis (mean: 5.5 mg/L, 14.4% subtherapeutic, 9.3% toxic) and other non-pulmonary infection (mean: 5.2 mg/L, 3.3% subtherapeutic, 16.5% toxic).

Conclusion: Linezolid serum concentrations are reduced in patients with pulmonary infections. Future studies should investigate if other linezolid thresholds are needed in those patients due to linezolid pooling in patients´ lung.