Safety of longer linezolid regimen in children with drug-resistant tuberculosis and extensive tuberculosis in Southwest China

Abstract

Objectives: Linezolid (LNZ) has recently been listed by the World Health Organization (WHO) as a Group A agent for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in longer regimens (18-20 months). However, little is known about the safety of LNZ in longer TB treatment regimens in children.

Methods: Here we report 31 children who received LNZ treatment for drug-resistant tuberculosis (DR-TB) and extensive tuberculosis in the Children's Hospital of Chongqing Medical University, China, during September 2016 to March 2019. The mean duration of LNZ treatment was 8.56 months (range, 1-24 months).

Results: Of the 31 patients, 13 (42%) had suspected or confirmed adverse events (AEs) related to LNZ treatment, including digestive symptoms, haematological toxicity, neuropathy and lactic acidosis. Haematological toxicity was the most frequent AE, presenting as leukopenia (9/13) and anaemia (5/13). No hepatotoxicity or nephrotoxicity was observed. Two patients suffered from life-threatening lactic acidosis when the LNZ dose was increased to 1.2 g daily, however they recovered following LNZ withdrawal.

Conclusion: A high rate of AEs of LNZ treatment was observed in children receiving a longer regimen, which might relate to the treatment course and dose. Haematological toxicity was the most frequent AE in children. It is necessary to regularly monitor the blood chemistry and lactic acid concentration during LNZ treatment.

Keywords: Adverse event; Drug-resistant tuberculosis; Linezolid; Safety.