Extract
To the Editor:
The world-wide increase in the incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) poses a major clinical challenge. The treatment outcome of MDR-TB and XDR-TB patients is often poor and unsuccessful in the absence of an optimal number of active drugs [1]. Novel antituberculous compounds are urgently required and only very few, such as bedaquiline, have recently been approved for tuberculosis treatment [2]. In a recent phase 2b clinical trial that was based on a 160 newly diagnosed MDR-TB patients, the addition of bedaquiline to a preferred background regimen for 24 weeks resulted in faster culture conversion and significantly more culture conversion at 120 weeks compared with the control group. However, there were more deaths in the bedaquiline than in the placebo group and half of these patients died due to tuberculosis. So far, it is unclear whether the death of any of these patients may have been associated with diminished susceptibility to bedaquiline[3].
Our study indicates that emergence of drug resistance to bedaquiline is already an ongoing threat, as we provide in vivo evidence of acquired resistance due to a mutation in an efflux pump-related gene, and its association with clofazimine and bedaquiline cross resistance in an
- Received August 4, 2014.
- Accepted September 20, 2014.
- ©ERS