Objective To explore the risk factors for acquired drug resistance among patients with new smear-positive pulmonary tuberculosis receiving anti-tuberculosis fixed-dose combination (FDC) preparations.

Methods A retrospective cohort study was conducted. Patients with newly-treated smear-positive pulmonary tuberculosis who received standardized treatment with FDC tablet (ethambutol hydrochloride, pyrazinamide, rifampicin and isoniazid tablets) at Shaoxing Central Hospital Medical Community General Hospital from January 2022 to December 2024 were enrolled. Sputum culture and drug susceptibility testing were performed before treatment initiation, at the end of the second month of treatment, and at the end of the sixth month of treatment. Multivariate Logistic regression was used to analyze factors associated with acquired drug resistance.

Results A total of 163 patients with fully drug-susceptible isolates at baseline were included, among whom 40 developed acquired drug resistance after treatment, with an acquired drug-resistance rate of 24.54%. The top three resistant drugs were isoniazid (19.02%), streptomycin (11.66%), and rifampicin (11.66%). Multivariate Logistic regression demonstrated that male sex[OR=1.92, 95%CI (1.06, 3.51)], treatment interruption ≥1 episode[OR=3.32, 95%CI (1.83, 6.02)], and bilateral lung involvement involving ≥3 lung fields[OR=2.19, 95%CI (1.19, 4.00)]were independent risk factors for acquired drug resistance during FDC treatment (allP<0.05).

Conclusion A considerable risk of acquired drug resistance still exists in initially drug‑susceptible patients with newly-treated smear-positive pulmonary tuberculosis treated with FDC. High-risk populations should be prioritized, and directly observed therapy should be strengthened to prevent treatment interruption.

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