Influence of Linezolid Clearance on the Induction of Thrombocytopenia and Reduction of Hemoglobin

Abstract

IntroductionAlthough linezolid (LZD) has proven effective for the treatment of infections caused by multidrug-resistant Gram-positive cocci, thrombocytopenia and anemia associated with reduced hemoglobin (Hb) levels are common side effects. To study the association between the development of these adverse effects and blood LZD levels, the authors evaluated the correlation between LZD clearance (LZD-CL), platelet (PLT) counts and Hb levels. MethodsSixteen patients with methicillin-resistant Staphylococcus aureus infection were administered LZD over a period of 4 to 41days, and blood was collected at variable time points beginning on day 4 (n=31). Blood LZD levels were measured by high-performance liquid chromatography, and LZD-CL was estimated by the population pharmacokinetics mean parameter and Bayesian methods. The relationship between the estimated LZD-CL and reductions in PLT counts and Hb levels was then evaluated by regression analysis. ResultsDuring the LZD treatment period, a weak correlation was identified between the LZD-CL rate and PLT counts (r2=0.31, n=31). Significantly, the regression analysis between LZD-CL and Hb levels showed a stronger correlation (r2=0.54, n=31), with Hb levels clearly decreasing with reductions in the LZD-CL rate. ConclusionsIn patients undergoing treatment with LZD, low LZD-CL rates correlated with reductions of both PLT counts and Hb levels, suggesting that increase of blood LZD levels influences hematopoietic function. Because a strong correlation was noted between LZD-CL and Hb levels, closely monitoring changes in Hb levels during treatment with LZD may detect the development of adverse effects such as thrombocytopenia and anemia.