Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with Gram-positive infections

Retrospective studies have documented a significant association between linezolid (LNZ) plasma concentrations and drug-related haematological toxicity. However, the safe upper threshold level for LNZ plasma trough concentrations (C-min values) has not been defined with certainty. A prospective observational study was performed aimed at comparing LNZ C-min values in patients developing drug-related side effects with those measured in patients not experiencing LNZ toxicity. LNZ C-min values were measured from the first week after starting therapy and were repeated periodically up to the end of treatment. Fifty patients, for a total of 210 LNZ C-min evaluations, were considered. All patients (n = 9) who developed drug-related haematological toxicity also had significantly higher plasma LNZ C-min values during the first week of therapy (9.0 +/- 6.4 mg/L vs. 4.9 +/- 3.7 mg/L; P < 0.01) and thereafter (9.3 +/- 5.4 mg/L vs. 4.4 +/- 3.4 mg/L; P < 0.01). The significant association between LNZ plasma concentrations and haematological toxicity was also confirmed by multivariate logistic regression analysis including age, serum creatinine and concomitant medications as independent variables. A causal relationship between LNZ concentrations and the risk of developing drug-related haematological toxicity was observed. Accordingly, application of therapeutic drug monitoring may improve the safety outcome of patients receiving LNZ therapy. (C) 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.