Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study

Abstract

Background Bedaquiline and delamanid offer the possibility of more effective and less toxic multidrug-resistant tuberculosis (MDR-TB) treatment. With this treatment, however, some patients, remain at high risk for an unfavorable treatment outcome. The endTB observational study is the largest multicountry cohort of patients with rifampin-resistant/MDR-TB treated in routine care, according to WHO guidance, with delamanid-and/or bedaquiline-containing regimens. We report frequency of sputum culture conversion within six-months of treatment initiation and risk factors for non-conversion. Methods We included patients with a positive baseline culture who initiated a first endTB regimen prior to April 2018. Two consecutive negative cultures collected > 15 days apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups. Findings 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%) or both (10%). Of these, 939 (85%) experienced culture conversion within six months. In adjusted analyses, patients with HIV had a lower probability of conversion (0•73 [95% CI: 0•62, 0•84]) than patients without HIV (0•84 [95% CI: 0•79, 0•90]; p=0•03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0•68 [95% CI: 0•57, 0•79]) relative to patients without either (0•89; 95% CI: 0•84, 0•95; p=0•0004). Hepatitis C infection, diabetes mellitus/glucose intolerance, and baseline resistance were not associated with conversion.

Interim Effectiveness and Safety Comparison of Bedaquiline-Containing Regimens for Treatment of Diabetic Versus Non-Diabetic MDR/XDR-TB Patients in China: A Multicenter Retrospective Cohort Study

“…Patients with HIV had lower probability of conversion than patients without HIV. Patients with HCV or DM/glucose intolerance were not associated with culture conversion [27].…”

Insignificant difference in culture conversion between bedaquiline-containing and bedaquiline-free all-oral short regimens for multidrug-resistant tuberculosis

“…Culture conversion at six months was 81% (25/31) in South Africa (Mohr et al, 2018), 89.4% (126/141) in South Korea (Kang et al, 2020), 97% (28/29) in French (Guglielmetti et al, 2015). In the endTB Observational Study with regimens containing bedaquiline (63%), delamanid (27%), or both (10%), 85% (939/1109) experienced culture conversion within six months (Franke et al, 2021). Our results (83.1% and 94.4% at two and four months) were similar to or better than those studies above.…”

Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial

“…The endTB observational study expanded the use of novel compounds (bedaquiline and delamanid) and repurposed older agents (linezolid and clofazimine) that had limited prior population exposure for TB. Delivered within longer and sometimes injectable-sparing regimens, preliminary results are encouraging [ 56 ]. Shorter regimens are the subject of other studies.…”