Abstract:

Objective To evaluate the efficacy and safety of 24-week bedaquiline (Bdq)-containing regimen on multidrug-resistant pulmonary tuberculosis and extensively drug-resistant pulmonary tuberculosis (MDR/XDR-PTB) patients and provide clinical evidence for further safe and effective use in more Chinese MDR/XDR-PTB patients. Methods Forty-four patients with mycobacterium culture-positive MDR-TB and XDR-TB were enrolled in Changsha Central Hospital Affiliated to University of South China from March 2018 to March 2020 and then treated with Bdq-containing regimen. Out of them, 31 were males and 13 were females with a median age of 38.2 (26, 49) years in the whole, while 25 with pulmonary cavities. The efficacy of the regimen was evaluated by culture conversion rates and pulmonary cavity closure rate at the end of 24 weeks, and the safety was evaluated by the incidence of adverse events, especially the occurrence of QT prolongation. Results Out of 44 patients, 38 achieved successful culture conversion, 2 failed sputum conversion, 2 died, 1 dropped out, and 1 lost to follow-up, with favorable outcome at 86.4% (38/44). Forty patients completed 24 weeks of Bdq treatment, and the culture conversion rates were 45.5% (20/44), 72.5% (29/40), 95.0% (38/40), 100.0% (40/40) and 95.0% (38/40) at the end of 2, 4, 8, 12 and 24 weeks, respectively, with the median conversion time at 22 days (interquartile range IQR18-59). Among the 25 patients with pulmonary cavities, 23 completed 24 weeks of treatment, and the rate of pulmonary cavity closure was 39.1% (9/23) and 82.6% (19/23) at the end of 12 and 24 weeks, respectively. Twenty-nine patients (65.9%, 29/44) reported a total of 81 adverse events (AEs), 72.8% (59/81) of which were grade 1 or 2.QT prolongation was the most common one probably associated with Bdq (40.9%,18/44). Conclusion Inclusion of Bdq in the regimen can achieve higher rates of culture conversion and cavity closure at the end of 24 weeks with acceptable safety profiles in MDR/XDR-TB patients.

Key words: Tuberculosis,pulmonary, Extensively drug-resistant tuberculosis, Tuberculosis,multidrug-resistant, Bedaquiline, Clinical protocols