Clinical Outcomes Among Patients With Drug-resistant Tuberculosis Receiving Bedaquiline- or Delamanid-Containing Regimens

Abstract

Background

Bedaquiline and delamanid are newly available drugs for treating multidrug-resistant tuberculosis (MDR-TB); however, there are limited data guiding their use and no comparison studies.

Methods

We conducted a prospective, observational study among patients with MDR-TB in Georgia who were receiving a bedaquiline- or delamanid-based treatment regimen. Monthly sputum cultures, minimal inhibitory concentration testing, and adverse event monitoring were performed. Primary outcomes were culture conversion rates and clinical outcomes. Targeted maximum likelihood estimation and super learning were utilized to produce a covariate-adjusted proportion of outcomes for each regimen.

Results

Among 156 patients with MDR-TB, 100 were enrolled and 95 were receiving a bedaquiline-based (n = 64) or delamanid-based (n = 31) regimen. Most were male (82%) and the median age was 38 years. Rates of previous treatment (56%) and cavitary disease (61%) were high. The most common companion drugs included linezolid, clofazimine, cycloserine, and a fluoroquinolone. The median numbers of effective drugs received among patients on bedaquiline-based (4; interquartile range [IQR], 4–4) and delamanid-based (4; IQR, 3.5–5) regimens were similar. Rates of acquired drug resistance were significantly higher among patients receiving delamanid versus bedaquiline (36% vs 10%, respectively; P < .01). Adjusted rates of sputum culture conversion at 2 months (67% vs 47%, respectively; P = .10) and 6 months (95% vs 74%, respectively; P < .01), as well as more favorable clinical outcomes (96% vs 72%, respectively; P < .01), were higher among patients receiving bedaquiline versus delamanid.

Conclusions

Among patients with MDR-TB, bedaquiline-based regimens were associated with higher rates of sputum culture conversion, more favorable outcomes, and a lower rate of acquired drug resistance versus delamanid-based regimens.

Abstract

In a prospective, observational, cohort study of patients receiving bedaquiline- versus delamanid-based regimens for multidrug-resistant tuberculosis, those receiving bedaquiline had higher rates of sputum culture conversion and favorable outcomes and were less likely to develop acquired drug resistance.