Abstract:

Objective: To evaluate the safety of the B-Pa-L/M regimen containing bedaquiline (Bdq), pretomanid (Pa), linezolid (Lzd), and/or moxifloxacin (Mfx) in elderly patients (≥65 years) with rifampicin-resistant pulmonary tuberculosis (RR-PTB). Methods: This prospective, multicenter, clinical cohort study was conducted from March to November 2025. According to the inclusion criteria, RR-PTB patients receiving the B-Pa-L/M regimen were enrolled from six designated tuberculosis medical institutions nationwide, including Xi’an Chest Hospital, Anhui Chest Hospital, Jiangxi Chest Hospital, Heilongjiang Provincial Infectious Disease Hospital, the Sixth People’s Hospital of Xinjiang Uygur Autonomous Region, and Beijing Chest Hospital, Capital Medical University. Patients were divided into an elderly group (≥65 years) and a control group (<65 years) using age 65 as the cutoff. All adverse events (AEs) during treatment, including myelosuppression, QTc interval prolongation, gastrointestinal reactions, neurological impairment, and hepatic injury, were collected and analyzed. The overall incidence of AEs, the incidence of grade ≥3 AEs, and the distribution of AE types were calculated. Results: A total of 51 patients were enrolled. Among them, 35 patients (68.6%) experienced 65 AE episodes (127.5%), and 8 patients (15.7%) developed 10 episodes (19.6%) of grade ≥3 AEs. Among the 22 patients in the elderly group, 18 (81.8%) experienced 35 AE episodes (159.1%), and 5 (22.7%) developed 7 episodes (31.8%) of grade ≥3 AEs. Among the 29 patients in the control group, 17 (58.6%) experienced 30 AE episodes (103.4%), and 3 (10.3%) developed 3 episodes (10.3%) of grade ≥3 AEs, no statistically significant differences were observed between the two groups in the overall incidence of AEs, the incidence of grade and the episode rate ≥3 AEs (all P>0.05). The incidence rates of bone marrow suppression, and other adverse events (number of cases/frequency) in the elderly group and the control group were 5 cases (22.7%) and 1 case (3.4%) per 10 frequency (45.5%) and 4 frequency (13.8%), and 4 cases (18.2%) and 1 case (3.4%) per 4 frequency (18.2%) and 1 frequency (3.4%), respectively, after Bonferroni correction, no significant differences were found in the incidence of two AE types between the two groups (all P>0.004). Regarding temporal distribution, QTc interval prolongation and gastrointestinal reactions predominantly occurred within the first 8 weeks of treatment, myelosuppression peaked at weeks 9-16, and neurological impairment was concentrated at weeks 17-24, and the distribution patterns in the elderly group were essentially consistent with those in the control group. Conclusion: Although the incidence of various AEs was higher in elderly RR-PTB patients treated with the B-Pa-L/M regimen compared to younger patients, these differences were not statistically significant; overall, the safety profile was favorable. In clinical practice, intensified monitoring strategies should still be implemented for elderly patients, particularly regarding the occurrence of myelosuppression, and therapeutic drug monitoring along with individualized dose adjustments should be performed when necessary, so as to minimize the risk of severe AEs while ensuring treatment efficacy.

Key words: Tuberculosis, pulmonary, Aged, Rifampin, Drug resistance, Program evaluation, B-Pa-L regimen