Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study

Abstract

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

Respiratory infection: insights from Assembly 10 of the European Respiratory Society 2017 Annual Congress

“…The results of this retrospective evaluation show that bedaquiline-containing regimens achieved high culture conversion and treatment success rates (11). This study also shows that patients put under BQ containing regimens are well tolerated and safe, as can also be concluded from other available evidence (12).…”

“…BQ was interrupted due to adverse events in 5.8% of cases. The most frequent adverse events in the study were nausea (31.5%), peripheral neuropathy (23.3%) and otovestibular toxicity (23.3%) (11). Ten percent of patients experienced QTcF prolongation >500 ms. A single case died, having electrocardiographic abnormalities that were probably non-BQ related (11).…”

“…They included patients who started treatment between January 1st, 2008 and August 30 th , 2016 (11). BQ had to be administered within an individualized TB regimen which was administered following results of drug susceptibility testing.…”

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…One patient died after having had electrocardiographic abnormalities, which were assumed notbedaquiline related. 54 Bedaquiline is used in the TB Alliance NIX-TB trial and appears useful in the treatment of XDR-TB, pre-XDR-TB, and treatment-intolerant or treatment-non-responsive MDR-TB. The NIX-TB trial is a single-arm, open-label trial of bedaquiline, pretomanid (formerly Pa-824), and linezolid (600 mg twice daily) given for six months, with an extra three months added if participants are sputum culture positive at four months.…”

Proposal for a standardised treatment regimen to manage pre- and extensively drug-resistant tuberculosis cases

“…The trial(s) should ideally be able to study the efficacy of the regimen even in patients with TB resistant to FQs and SLIs, and evaluate its ideal duration; 2) more evidence on bedaquiline and delamanid safety when used for >6 months and programmatically [61] is necessary, as these two drugs are core pillars of the proposed regimen; 3) evidence on safety and efficacy of bedaquiline and delamanid combination is also necessary; 4) finally, the different programmatic and operational aspects of using a similar regimen need to be properly studied.…”