Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid: A Prospective Multi-country Study.

Auteurs: Franke MF Khan P Hewison C Khan U Huerga H Seung KJ Rich ML Zarli K Samieva N Oyewusi L Nair P Mudassar M Melikyan N Lenggogeni P Lecca L Kumsa A Khan M Islam S Hussein K Docteur W Chumburidze N Berikova E Atshemyan H Atwood S Alam M Ahmed S Bastard M Mitnick CD
Référence de l'article: American journal of respiratory and critical care medicine 2020 Jul 24; (); Array. doi: 10.1164/rccm.202001-0135OC. Epub 2020 07 24
extensively drug-resistant tuberculosis interim outcome multidrug-resistant tuberculosis rifampicin-resistant tuberculosis sputum conversion


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. Interpretation Frequent sputum conversion in patients with rifampin-resistant/MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.