Efficacy and safety study of different doses of linezolid in combination with bedaquiline in the treatment of drug-resistant pulmonary tuberculosis.

Abstract

Introduction: Drug-resistant tuberculosis presents a major global health challenge due to limited therapeutic options and significant toxicity of traditional regimens. Linezolid, a core Group A drug per WHO guidelines, demonstrates high efficacy but its optimal dosing is debated due to dose-dependent adverse effects. This study aimed to evaluate the efficacy and safety of different initial doses linezolid in combined with bedaquiline for treating drug-resistant pulmonary tuberculosis.

Methods: This retrospective study analyzed patients with drug-resistant tuberculosis treated with bedaquiline and linezolid in China, June 2019-June 2022. Data originated from medical records. Adverse Drug Reactions (ADRs) were categorized using the Common Terminology Criteria for Adverse Events (v5.0). Three groups were formed based on initial linezolid dose: 1200 mg/d (high-dose, n=99), 600 mg/d (low-dose, n=121), and 0 mg/d (control, n=50). Clinical data, epidemiological characteristics, treatment outcomes, adverse events, and prognoses of these groups were compared and analyzed statistically.

Results: Our research scrutinized the effects of different initial doses of linezolid and bedaquiline on drug-resistant tuberculosis. No significant differences were noted between high-dose and low-dose groups in 6 months sputum smear negativity, cavitary closure time or time for lesion resorption and reduction. However, a higher incidence of adverse events was observed in the high-dose group (47.47%) compared to the low-dose group (29.75%), with bone marrow suppression, peripheral neuropathy, and optic neuritis being predominant. Notably, the proportion of patients requiring dose adjustment due to adverse events was significantly higher in the high-dose group (74.47%) than in the low-dose group (50%, P=0.021).

Conclusions: Initial daily linezolid dose of 600 mg and 1,200 mg in combination with bedaquiline yield equivalent efficacy for drug-resistant pulmonary tuberculosis. The lower dose demonstrated improved tolerability. For the said therapy, we advocate a primary recommendation of a daily linezolid dose of 600 mg.