High plasma linezolid concentration and impaired renal function affect development of linezolid-induced thrombocytopenia

Thrombocytopenia is sometimes observed during linezolid therapy. Here, we aimed to investigate the factors affecting linezolid-induced thrombocytopenia. A prospective observational study was performed between October 2009 and February 2011; 30 patients were included. Plasma linezolid trough concentrations were measured on days 3, 7 and 14 after initial drug administration. Platelet counts and haemoglobin levels were also monitored. Thrombocytopenia occurred in 17 patients (56.7). Median linezolid trough concentrations on day 3 were significantly higher in patients with renal impairment (creatinine clearance 60 mL/min) than in patients without renal impairment (14.7 versus 4.8 mg/L; P0.0001). Median linezolid trough concentrations on day 3 in patients who developed thrombocytopenia were also significantly higher than those in patients who did not (13.4 versus 4.3 mg/L, P0.0001). Development of thrombocytopenia occurred significantly more frequently in patients with linezolid trough concentration 7.5 mg/L (OR, 90.0; P0.0001) and renal impairment (OR, 39.0; P0.0002). The KaplanMeier plot showed that the median time from the initiation of therapy to development of thrombocytopenia was 11 days. Patients with renal impairment are more likely to have a high plasma linezolid concentration. In addition, a high plasma linezolid concentration and renal impairment significantly affected the development of linezolid-induced thrombocytopenia. Further studies are required to evaluate whether therapeutic drug monitoring-guided dosage adjustment of linezolid decreases the adverse effects while maintaining treatment efficacy in patients with renal dysfunction.