Rapid emergence of Mycobacterium tuberculosis bedaquiline resistance: lessons to avoid repeating past errors

• Published in: The European respiratory journal Vol. 49; no. 3; p. 1601719
• Main Authors: Veziris, Nicolas, Bernard, Christine, Guglielmetti, Lorenzo, Le Du, Damien, Marigot-Outtandy, Dhiba, Jaspard, Marie, Caumes, Eric, Lerat, Isabelle, Rioux, Christophe, Yazdanpanah, Yazdan, Tiotiu, Angelica, Lemaitre, Nadine, Brossier, Florence, Jarlier, Vincent, Robert, Jerome, Sougakoff, Wladimir, Aubry, Alexandra
• Format: Journal Article
• Language: English
• Published: England European Respiratory Society Journals Ltd 01.03.2017
• Subjects: Clofazimine; Cross-resistance; Multidrug resistance; Mutation; Mycobacterium tuberculosis; Tuberculosis
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/13993003.01719-2016

Bedaquiline (BDQ) has demonstrated potent clinical activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis complex strains [1–3]. It has now been used in >50 countries, and it is estimated that ∼2500 patients had been treated with BDQ by the end of 2015. In spite of its recent clinical use, there are few reports of BDQ-resistant strains [4, 5]. Mutations in the rv0678 gene encoding the MmpL5 efflux pump repressor generate low-level BDQ resistance and clofazimine (CFZ) cross-resistance [6]. To our knowledge, this is the sole mechanism of BDQ resistance described in clinical strains [4, 5]. Despite its introduction in France in 2011 for XDR- and MDR-tuberculosis (TB) treatment, we report herein four BDQ-resistant cases, and discuss strategies to avoid a surge of BDQ resistance.