2017•European Respiratory JournalOpen access
Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study
Borisov Se, Keertan Dheda, Martin Enwerem, Rodolfo Romero Leyet, Lia D’Ambrosio, Rosella Centis, Giovanni Sotgiu, Simon Tiberi, Jan‐Willem C. Alffenaar, А. O. Мaryandyshev, Evgeny Belilovski, Shashank Ganatra, Alena Skrahina, Onno W. Akkerman, Alena Aleksa, Rohit Amale, Janina Artsukevich, Judith Bruchfeld, José A. Caminero, Isabel Carpena Martinez, Luigi Ruffo Codecasa, Margareth Pretti Dalcolmo, Justin T. Denholm, Paul Douglas, Raquel Duarte, Aliasgar Esmail, Mohammed Fadul, Filippov Av, Lina Davies Forsman, Mina Gaga, Julia-Amaranta García-Fuertes, José-María García-García, Gina Gualano, Jerker Jonsson, Heinke Kunst, Jillian S. Y. Lau, Barbara Lazaro Mastrapa, Jorge Lazaro Teran Troya, Selene Manga, Κaterina Manika, Pablo González Montaner, Jai Mullerpattan, Suzette Oelofse, Martina Ortelli, Domingo Palmero, Fabrizio Palmieri, Antonella Papalia, Apostolos Papavasileiou, Marie-Christine Payen, Emanuele Pontali, Carlos Robalo Cordeiro, Laura Saderi, Tsetan Dorji Sadutshang, Tatsiana Sanukevich, Varvara Solodovnikova, Antonio Spanevello, Sonam Topgyal, Federica Toscanini, Adrian R Tramontana, Zarir Udwadia, Pietro Viggiani, Verónica White, Alimuddin Zumla, Giovanni Battista Migliori
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.