High treatment success rate for multidrug-resistant and extensively drug-resistant tuberculosis using a bedaquiline-containing treatment regimen

Abstract

South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria.PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.9%) had XDR-TB, 99 (49.3%) were female and the median age was 34 years (interquartile range (IQR) 27–42). 134 (67.0%) were living with HIV; the median CD4+ count was 281 cells·μL−1 (IQR 130–467) and all were on antiretroviral therapy.16 out of 200 patients (8.0%) did not complete 6 months of bedaquiline: eight were lost to follow-up, six died, one stopped owing to side effects and one was diagnosed with drug-sensitive TB. 146 out of 200 patients (73.0%) had favourable outcomes: 139 (69.5%) were cured and seven (3.5%) completed treatment. 25 patients (12.5%) died, 20 (10.0%) were lost from treatment and nine (4.5%) had treatment failure. 22 adverse events were attributed to bedaquiline, including a QT interval corrected using the Fridericia formula (QTcF) >500 ms (n=5), QTcF increase >50 ms from baseline (n=11) and paroxysmal atrial flutter (n=1).Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this preXDR-TB and XDR-TB cohort.

Bedaquiline, moxifloxacin, pretomanid, and pyrazinamide during the first 8 weeks of treatment of patients with drug-susceptible or drug-resistant pulmonary tuberculosis: a multicentre, open-label, partially randomised, phase 2b trial

“…There is already evidence that rifampicin-resistant tuberculosis regimens containing bedaquiline can achieve success rates of 77% and reduce disease-associated mortality. 21,22 The rapid fall in the rifampicin-resistant tuberculosis bacillary load seen in the time to culture negativity analysis in MGIT suggests a potent sterilising effect and also the potential for BPaMZ to shorten the duration of treatment for drug-susceptible tuberculosis.…”

Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

“…Over the past 2 years, a series of reports showed that treatment outcomes in patients with drug-resistant TB could be improved using new combinations of drugs given for shorter periods of time, better selecting the "old" drugs to include in the treatment regimen or introducing new drugs for prolonged periods of time [15,[22][23][24][25][26][27].…”

Validation of Bedaquiline Phenotypic Drug Susceptibility Testing Methods and Breakpoints: a Multilaboratory, Multicountry Study

“…Bedaquiline (BDQ) is a diarylquinoline antimycobacterial agent that acts differently from other anti-TB agents through inhibiting ATP synthase, leading to ATP depletion and decreased mycobacterial survival; it also has bactericidal and sterilizing properties (3). In the treatment of MDR-TB, outcomes have considerably improved with the use of BDQ-based regimens (4)(5)(6)(7). A number of resistance-associated variants (RAVs) that may decrease susceptibility to BDQ have been reported.…”