Linezolid-Associated Neuropathy in Patients with MDR/XDR Tuberculosis in Shenzhen, China

Abstract

Objective

Linezolid is one of the key drugs for the treatment of multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB). We aimed to describe the incorporation of the Michigan Neuropathy Screening Instrument (MNSI) and serum trough concentration as screening tools for neurotoxicity in the management of MDR/XDR-TB patients receiving a linezolid-based treatment regimen in Shenzhen, China.

Methods

A total of 73 patients on a linezolid-containing anti–MDR/XDR-TB regimen were prospectively enrolled. The MNSI was used for peripheral neuropathy screening. Optic neuropathy was diagnosed by ophthalmologists. Serum trough concentration was recorded and its relationship with neuropathy analyzed.

Results

Of all patients, neuropathy was observed in 40% (29) during anti-TB treatment. Of these, 20 (69%) had peripheral neuritis, seven (24%) optic neuritis, and two (7%) both. Serum trough concentration >2 mg/L was observed in 17 (59%) patients with neuropathy and 13 (30%) patients without neuropathy. There was a significant statistical difference between the two groups (P=0.013). Time to onset of neuropathy from initiation of the linezolid-containing regimen was within 2 months for eight (28%) patients, 2–6 months for 18 (62%) patients, and >6 months for three (10%) patients. Sixteen (55%) patients were adjusted to a lower dose of 300 mg linezolid daily. Four (14%) patients had linezolid permanently removed from their regimen.

Conclusion

Neuropathy is a commonly reported adverse event associated with long-term use of linezolid. MNSI and serum trough–concentration monitoring can be adopted as simple screening tools for early detection of neuropathy to balance linezolid efficacy and tolerability.

Keywords:

• linezolid
• MDR/XDR-TB
• neuropathy
• MNSI
• serum trough concentration

Acknowledgments

We appreciate our patients and their families for their trust and consent to participate in this study. We thank all the physicians involved in the management and care of our patients, particularly the ophthalmic team, for their professional opinions. We also thank Youli Jiang for helping us with the manuscript.

Disclosure

The authors declare no conflicts of interest in this study.

Additional information

Funding

This study was funded by the Yangfan Foundation (2018KYJJ003), Summit Plan for Foshan High-level Hospital Construction (No. FSSYKF-2020001), Project funded by Shenzhen Third People's Hospital (No. G2021023) and the Technology Project of Guangdong Province (2020B1111170014), which are government funding schemes for the research of tuberculosis treatment and control.