Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients

Methods: We performed a retrospective study of patients who had trough (Cmin) and peak (Cmax) plasma levels measured during prolonged linezolid treatment. Dosage adjustments were performed when Cmin ≥10 mg/L and/or AUC24 ≥400 mg/L.h. Patients were divided into two subgroups according to the absence or presence of co-treatment with rifampicin (the linezolid group and the linezolid +rifampicin group, respectively). Data on demographic characteristics, disease, microbiology and haematochemical parameters were collected and outcomes in relation to drug exposure were compared between groups. Results: A total of 45 patients were included. Dosage adjustments were needed in 40% versus 0% of patients in the linezolid group (n¼35) versus the linezolid+rifampicin group (n¼10), respectively. Patients in the linezolid group had either significantly higher Cmin [3.71 mg/L (1.43‐6.38) versus 1.37 mg/L (0.67‐2.55), P,0.001] or AUC24 [212.77 mg/L.h (166.67‐278.42) versus 123.33 mg/L.h (97.36‐187.94), P,0.001]. Thrombocytopenia appeared in 51.4% versus 0% of cases in the linezolid group versus the linezolid+rifampicin group, respectively. In 33.3% of those patients who were experiencing thrombocytopenia, therapeutic drug monitoring (TDM)guided dosage reductions allowed recovery from toxicity and prosecution of therapy with good outcome. A logistic regression model for thrombocytopenia estimated a probability of 50% in the presence of Cmin of 6.53 mg/L and/or of AUC24 of 280.74 mg/L.h. Conclusions: MaintenanceovertimeofCminbetween2and7 mg/Land/orofAUC24between160and300 mg/L.h may be helpful in improving safety outcomes while retaining appropriate efficacy in adult patients receiving prolonged linezolid treatment.