关键词: 结核,肺, 抗药性, 抗结核药, 治疗应用, 药物评价

Abstract:

Objective: To evaluate the clinical safety of extended delamanid use beyond 6 months in patients with multidrug-resistant/rifampicin-resistant pulmonary tuberculosis (MDR/RR-TB). Methods: This retrospective study included 49 patients diagnosed with MDR/RR-TB and treated with a delamanid-based regimen at Beijing Chest Hospital, Capital Medical University, between January 2022 and December 2023. Patients were categorized into a conventional group (≤6 months; 29 cases) and an extended group (>6 months; 20 cases) based on the duration of delamanid use. Data collected included epidemiological history (e.g., tuberculosis exposure history), demographic characteristics (e.g., age, gender), information on adverse drug reactions, electrocardiogram (ECG) results before and after treatment, clinical features (e.g., medication details), and other relevant parameters. The incidence of adverse drug reactions was compared between the two groups. Results: In the conventional group, the average QTc interval increased with the duration of treatment, peaking at 5 months (421 ms) before subsequently decreasing. Similarly, in the extended group, the average QTc interval rose during treatment, reaching a peak at 3 months (450 ms), then elevated again to 448 ms at 8 months before declining. The total incidence of adverse drug reactions in the extended group was 85.0% (17/20), significantly higher than that in the conventional group (58.6%, 17/29), with a statistically significant difference (χ²=3.878, P=0.049). Additionally, 60.0% (12/20) of patients in the extended group exhibited QTc intervals between 450 and 500 ms, significantly exceeding the rate observed in the conventional group (27.6%, 8/29), with a statistically significant difference (χ²=5.148, P=0.023). Among patients in the extended group with abnormal electrocardiograms, the duration of delamanid use ranged from 2 to 9 months, with a mean duration of 3.8±0.7 months. Neither group experienced adverse cardiac events or required medication discontinuation. Additionally, there were no significant differences between the two groups in the incidence of adverse reactions, including QTc interval ≥500 ms, alanine aminotransferase/aspartate aminotransferase abnormalities, bilirubin abnormalities, myocardial enzyme abnormalities, gastrointestinal reactions, or insomnia. Conclusion: Delamanid shows potential for extended use beyond 6 months while maintaining a favorable safety profile. However, comprehensive evaluation prior to treatment and meticulous monitoring during the treatment process are essential to ensure patient safety.

Key words: Tuberculosis, pulmonary, Drug resistance, Antitubercular agents, Therapeutic applications, Drug evaluation