Efficacy and Safety Study of Different Doses of Linezolid in Combination with Bedaquiline in the Treatment of Drug-Resistant Pulmonary Tuberculosis.

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 of linezolid 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 from June 2019-June 2022. The data originated from medical records. Adverse drug reactions were categorized using the Common Terminology Criteria for Adverse Events (v5.0). Three groups were formed based on the initial linezolid dose: 1,200 mg/day (high-dose, n = 99), 600 mg/day (low-dose, n = 121), and 0 mg/day (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 for 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 myelosuppression, peripheral neuritis, 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 yields equivalent efficacy for drug-resistant pulmonary tuberculosis. The lower dose demonstrates improved tolerability. For the said therapy, we advocate a primary recommendation of a daily linezolid dose of 600 mg.