Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety.

BACKGROUND: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). METHODS: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

[Study on the genotype of Mycobacterium tuberculosis isolates from hospitals in Tianjin].

OBJECTIVE: To explore the characteristics on molecular epidemiology of Mycobacterium tuberculosis isolates from hospitals in Tianjin area. METHODS: One hundred M. tuberculosis isolated strains were collected in succession from August 16th-December 25th, 2005 in Tianjin Haihe Hospital and genotyped by spoligotyping and multiple locus variable number-tandem repeat(VNTR). Data was analyzed by cluster software. Based on the concept of Beijing lineage, it was determinate two sub-groups: atypical Beijing strains and W strain/typical family strains by multiplex and real-time PCR. The associations of subgroups with drug resistance and age were assessed by the chi2 test. RESULTS: 96 M. tuberculosis strains were genotyped in which 91.7% (88/96) strains belonged to Beijing genotype (including 3 Beijing-like strains) by spoligtyping. VNTR typing could differentiate 60 genotypes among the 88 Beijing genotype strains. 93.2% of the Beijing lineage M. tuberculosis strains of this study belonged to W strain/typical Beijing family strains (82/88). No statistically significant differences were observed in the proportions of the two sub-groups in patients of different age, or drug resistance (P > 0.05). CONCLUSION: The M. tuberculosis Beijing genotype strains were dominated on tuberculosis hospital patients of Tianjin area. The discriminatory power of VNTR typing was higher than that of spoligtyping. The two sub-groups of Beijing lineage had been prevalent in Tianjin, however W strain/typical Beijing family strains were of preponderance.