Risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy

Abstract

The major adverse event associated with linezolid treatment is thrombocytopenia. This study investigated risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy. This was a retrospective study of patients treated with linezolid 600 mg q12h, by the oral or parenteral route, between July 2007 and June 2009. Thrombocytopenia was defined as a ≥ 10 × 10⁴ cells/mm³ decrease from the baseline or a ≥ 30% reduction. Thirty-three variables were analyzed as risk factors associated with thrombocytopenia. Multivariate analysis was performed with SPSS version 16 software. This study included 331 patients (221 male, 58.0 ± 20.2 years). The mean duration of linezolid therapy was 10.5 ± 8.7 days. Thrombocytopenia occurred in 128 patients (38.7%), of whom 21 required platelet transfusion. Thrombocytopenia developed 7.4 ± 4.8 days after linezolid initiation, and the platelet count recovered 12.3 ± 7.8 days after withdrawal. In the final steps of stepwise logistic regression analysis, 5 variables were selected: duration of linezolid therapy ≥ 14 days [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.73-5.34, P < 0.001], creatinine clearance < 50 mL/min (OR 2.32, 95% CI 1.45-3.74, P < 0.001), chronic liver disorders (OR 1.63, 95% CI 0.92-2.86, P = 0.092), and respiratory tract infections (OR 1.75, 95% CI 1.05-2.91, P = 0.031). In contrast to findings with parenteral administration, oral administration of linezolid decreased the risk of thrombocytopenia (OR 0.38, 95% CI 0.15-0.97, P = 0.042). The time to the onset of thrombocytopenia in patients with creatinine clearance <50 mL/min was significantly shorter than that in patients with creatinine clearance ≥ 50 mL/min (6.7 ± 4.4 and 8.5 ± 5.2 days, P = 0.039), and in patients administered orally the time to the onset of thrombocytopenia was 10.4 ± 6.6 days. Several factors influenced the occurrence of linezolid-induced thrombocytopenia. Dose adjustment may be required in at-risk patients, especially those with renal dysfunction.