Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs

Huerga H. Khan U. Bastard M. Mitnick C.D. Lachenal N. Khan P.Y. Seung K.J. Melikyan N. Ahmed S. Rich M.L. Varaine F. Osso E. Rashitov M. Salahuddin N. Salia G. Sánchez E. Serobyan A. Siddiqui M.R. Tefera D.G. Vetushko D. Yeghiazaryan L. Holtzman D. Islam S. Kumsa A. Leblanc G.J. Leonovich O. Mamsa S. Manzur-Ul-Alam M. Myint Z. Padayachee S. Franke M.F. Hewison C.
15 October 2022 Oxford University Press

Clinical Infectious Diseases
2022 #75 Issue 8 1307 - 1314 pp.

Background. Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs. Methods. We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented. Results. Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 patients (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died, and 7.2% experienced treatment failure. Conclusions. Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.

adverse events , combination therapy , endTB , linezolid

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Field Epidemiology Department, Epicentre, Paris, France
Interactive Research and Development (IRD) Global, Singapore, Singapore
Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, United States
Partners In Health, Boston, MA, United States
Division of Global Health Equity, Brigham and Women’s Hospital, Boston, MA, United States
Pharmacovigilance Unit, Médecins Sans Frontières, Geneva, Switzerland
Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
Interactive Research and Development (IRD), Karachi, Pakistan
Medical Department, Médecins Sans Frontières, Paris, France
Partners In Health, Almaty, Kazakhstan
Indus Hospital and Health Network (IHHN), Karachi, Pakistan
Medical Department, Médecins Sans Frontières, Tbilisi, Georgia
Hospital Nacional Sergio Bernales Hospital, Lima, Peru
Medical Department, Médecins Sans Frontières, Yerevan, Armenia
Institute of Chest Diseases (ICD), Kotri, Pakistan
Partners In Health, Sierra Leone, Sierra Leone
The Republican Scientific and Practical Centre for Pulmonology and TB, Minsk, Belarus
National Center for Pulmonology, Yerevan, Armenia
Partners In Health, Maseru, Lesotho
Ministry of Health, Ethiopia
Zanmi Lasante, Cange, Haiti
Medical Department, Médecins Sans Frontières, Minsk, Belarus
Interactive Research and Development (IRD), Dhaka, Bangladesh
National Tuberculosis Program central, Yangon branch, Myanmar
Interactive Research and Development (IRD), Durban, South Africa

Field Epidemiology Department
Interactive Research and Development (IRD) Global
Department of Global Health and Social Medicine
Partners In Health
Division of Global Health Equity
Pharmacovigilance Unit
Clinical Research Department
Interactive Research and Development (IRD)
Medical Department
Partners In Health
Indus Hospital and Health Network (IHHN)
Medical Department
Hospital Nacional Sergio Bernales Hospital
Medical Department
Institute of Chest Diseases (ICD)
Partners In Health
The Republican Scientific and Practical Centre for Pulmonology and TB
National Center for Pulmonology
Partners In Health
Ministry of Health
Zanmi Lasante
Medical Department
Interactive Research and Development (IRD)
National Tuberculosis Program central
Interactive Research and Development (IRD)

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