Abstract

This retrospective cohort study investigated the effects of an initially reduced linezolid dosing regimen in hemodialysis patients through therapeutic drug monitoring (TDM). Patients were divided into two groups depending on their initial dose of linezolid (standard dose of 600 mg every 12 h or initially reduced dose of 300 mg every 12 h/600 mg every 24 h). The cumulative incidence rates of thrombocytopenia and severe thrombocytopenia were compared between both groups using the Kaplan–Meier method and log-rank test. Eleven episodes of 8 chronic hemodialysis patients were included; 5 were in the initially reduced-dose group. Thrombocytopenia developed in 81.8% of patients. The cumulative incidence rates of thrombocytopenia and severe thrombocytopenia in the initially reduced-dose group were significantly lower than in the standard-dose group (p < 0.05). At the standard dose, the median linezolid trough concentration (Cmin) just before hemodialysis was 49.5 mg/L, and Cmin at the reduced doses of 300 mg every 12 h and 600 mg every 24 h were 20.6 mg/L and 6.0 mg/L, respectively. All five episodes underwent TDM in the standard-dose group required dose reduction to 600 mg per day. Our findings indicate that initial dose reduction should be implemented to reduce the risk of linezolid-induced thrombocytopenia among hemodialysis patients.

Highlights

  • Studies have shown that a linezolid trough concentration of >7–8 mg/L is associated with an increased risk of thrombocytopenia

  • We recently demonstrated that therapeutic drug monitoring (TDM) and TDM-guided dose modifications might be beneficial in preventing treatment failure of non-dialysis dependent patients with creatinine clearance (CLCR ) < 60 mL/min [13]

  • Hemodialysis is a significant means of linezolid elimination in patients with end-stage renal disease (ESRD), as approximately 30% of the administered dose is removed during a 3 h hemodialysis session [14]

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Thrombocytopenia is the most common adverse effect of linezolid treatment. Studies have shown that a linezolid trough concentration of >7–8 mg/L is associated with an increased risk of thrombocytopenia. This often limits its clinical use and may lead to discontinuation of treatment [1]. This adverse event can increase the risk of mortality among critically ill patients [2,3]

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