Rapid emergence of Mycobacterium tuberculosis bedaquiline resistance: lessons not to repeat past errors

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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

Edité par CCSD ; European Respiratory Society -

On behalf of the CNR MyRMA and the Tuberculosis Consilium of the CNR MyRMA. International audience. 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.

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