Rhabdomyolysis in a Patient Treated With Linezolid for Extensively Drug-Resistant Tuberculosis

Abstract

Linezolid (Zyvox), an oxazolidinone antibiotic that is widely used for gram-positive infections, is increasingly being used for highly drug-resistant tuberculosis, although it is not approved for this use by any regulatory body. In case reports and series, linezolid seems to be useful for the treatment of both multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. These reports have revealed that certain side effects are common with the long-term use of linezolid, especially optic and peripheral neurologic and hematologic toxicities [1]. To better understand the clinical usefulness and toxicity of linezolid treatment for patients with tuberculosis, we are performing a prospective, institutional review board–approved study, entitled “A Phase IIa, Randomized, Two-Arm, Open-label, Clinical Trial of the Efficacy of Linezolid Combined with Antituberculous Therapy in Subjects with Extensively Drug-Resistant (XDR) Pulmonary Tuberculosis” (ClinicalTrials.gov registry number {type:clinical-trial,attrs:{text:NCT00727844,term_id:NCT00727844}}NCT00727844). All subjects receive and sign an informed consent document prior to enrollment. In this study, subjects are randomly allocated to receive 600 mg linezolid daily, either immediately or following a 2-month delay, until sputum smear conversion or therapy is received for 4 months, whichever comes first. Subjects then undergo a second randomization in which one group continues to receive 600 mg of linezolid daily and the other group receives therapy deescalated to a dose of 300 mg daily. Linezolid treatment is continued for 18–24 months after culture conversion. Here, we describe a case of recurrent rhabdomyolysis related to the use of linezolid in a subject enrolled in this trial.