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.