Linezolid-Associated Neurologic Adverse Events in Patients with Multidrug-Resistant Tuberculosis, France

Abstract

Linezolid is one of the most effective drugs for treating multidrug-resistant tuberculosis (MDR TB), but adverse effects remain problematic. We evaluated 57 MDR TB patients who had received >1 dose of linezolid during 2011-2016. Overall, patients received 600 mg/day of linezolid for a median of 13 months. In 33 (58%) patients, neurologic or ophthalmologic signs developed, and 18 (32%) had confirmed peripheral neuropathy, which for 78% was irreversible at 12 months after the end of TB treatment despite linezolid withdrawal. Among the 19 patients who underwent ophthalmologic evaluation, 14 patients had optic neuropathy that fully reversed for 2. A total of 16 (33%) of 49 patients had a linezolid trough concentration >2 mg/L, and among these, 14 (88%) experienced adverse effects. No significant association was found between trough concentration and neurologic toxicity. These findings suggest the need to closely monitor patients for neurologic signs and discuss optimal duration of linezolid treatment.

Keywords: France; MDR TB; TB; Tuberculosis; XDR TB; linezolid; neurologic events; neuropathy; pharmacokinetics; tuberculosis and other mycobacteria.

Figure 1

Outcomes for 65 patients with multidrug-resistant tuberculosis (MDR TB) admitted to Pitié-Salpêtrière Hospital, Paris, France, and included in study of linezolid-associated neurologic adverse events.

Figure 2

Peripheral neuropathy occurrence and evolution among the 57 patients who received linezolid for multidrug-resistant tuberculosis during 2011 and 2016, France. EMG, electromyelogram; NCV, nerve-conduction velocity testing; TB, tuberculosis.