Effectiveness and safety of bedaquiline-containing regimens for treatment on patients with refractory RR/MDR/XDR-tuberculosis: a retrospective cohort study in East China

Abstract

Objective Refractory rifampicin-resistant/multidrug resistant/extensively-drug resistant tuberculosis (RR/MDR/XDR-TB) were defined as patients infected with Mycobacterium tuberculosis (MTB) resistant to rifampicin(RR-TB), or at least resistant to rifampicin and isoniazid (MDR-TB) or added resistant to fluoroquinolones (FQs) and one of second line injectable agents (XDR-TB), a patient for whom an effective regimen (fewer than 4 effective agents due to adverse events (AEs) or multiple drug resistances) cannot be developed. To compare the effectiveness and safety of bedaquiline (BDQ)-containing and BDQ-free regimens for treatment of patients with refractory RR/MDR/XDR-TB. Methods Patients with refractory RR/MDR/XDR-TB receiving BDQ-containing regimens (BDQ group, n = 102) and BDQ-free regimens (non-BDQ group, n = 100) satisfied with included criteria were strictly included in this retrospective historical control study across East China. Culture conversion, treatment outcome, cavity closing rate, and AEs were compared between two groups. Results The baseline characteristics involved all possible aspects of patients were well balanced between two groups (p > 0.05). Culture conversion rates in the BDQ group at month 3 (89.2% vs. 66.0%), month 6 (90.2% vs 72.0%), month 9 (91.2% vs. 66.0%), and month 12 (94.1% vs 65.0%) were all significantly higher than those in non-BDQ group (p < 0.001). Similar results were observed in the cavity closing rate at month 9 (19.6% vs 8.0%, p = 0.0) and month 12 (39.2% vs 15.0%, p < 0.001). Patients receiving BDQ-containing regimens had more treatment success than those receiving BDQ-free regimens (p < 0.001; cure rate, 69.6% vs. 45.0%; complete the treatment, 22.5% vs. 18.0%; treatment success, 92.2% vs. 63.0%); the use of BDQ and combined with Linezolid or Clofazimine or Cycloserine were identified as independent predictors of treatment success and no culture reversion (P < 0.05). AEs were similarly reported in 26.5% of patients in the BDQ group and 19.0% in the non-BDQ group (p = 0.2). Conclusions BDQ-containing regimens resulted in better treatment outcomes and similar safety relative to BDQ-free regimens for patients with refractory pulmonary RR/MDR/XDR-TB.

Efficacy and safety of bedaquiline containing regimens in patients of drug-resistant tuberculosis: An updated systematic review and meta-analysis

“…In total, 41 studies are included in the updated version of this review. The studies [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] were divided into two groups: 36 observational studies including a total of 9,934 patients, and 5 experimental studies including a total of 468 patients. The patient’s mean age was 36.2 years.…”

“…A meta -analysis was conducted in 2021 that pooled the results of these studies [21] . However, results from additional well-designed observational and experimental studies were published [19] , [20] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] . To better analyze the effectiveness and safety of bedaquiline in MDR-TB, we conducted an updated meta -analysis.…”

Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis

“…Indeed, numerous clinical studies confirm that the strong bactericidal and sterilizing activity of BDQ-containing regimen originally found in mouse models of TB ( 123 , 124 ). BDQ has demonstrated potent clinical activity against MDR-and XDR-TB complex strains ( 27 , 118 , 121 , 122 ). Importantly, BDQ-containing treatment regimens have showed improved outcomes rate over SLID-containing regimens for the treatment of patients with RR-/MDR-TB ( 120 ).…”

At Long Last: Short, All-Oral Regimens for Multidrug-Resistant Tuberculosis in the United States

“…Moreover, by 2019, injectable agents were no longer favorable due to their substantial toxicity and were only recommended for use when other options were not available [ 29 ]. Success rates between 75% and 89% have been reported with all-oral bedaquiline-containing regimens [ 30 , 31 ]. Despite the alteration in regimen composition, the 2019 guidelines continued to recommend an 18- to 20-month treatment duration for the all-oral regimen in addition to the short injectable WHO regimen.…”