In vivo microevolution of Mycobacterium tuberculosis and transient emergence of atpE_Ala63Pro mutation during treatment in a pre-XDR TB patient

Bedaquiline a novel anti TB drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) recommended by the World Health Organization (WHO) [1] and recently upgraded to Group A drugs as one of the three key drugs along with linezolid and fluoroquinolones to be included in all MDR-TB regimens. Based on this grouping of second line drugs, the extensively drug resistant (XDR) TB is redefined as MDR/RR-TB that is resistant to a fluoroquinolone and to either bedaquiline or linezolid or both. Moreover bedaquiline in combination with pretomanid and linezolid is a part of BPaL regimen recommended for treating adult pulmonary TB patients having pre-XDR TB or MDR-TB which is either non-responsive or -intolerant to recommended standard treatment [2]. However globally emerging resistance to bedaquiline threatens the effectiveness of novel treatment regimens for drug resistant TB. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Arash Ghodousi has nothing to disclose. Conflict of interest: Alamdar Hussain Rizvi has nothing to disclose. Conflict of interest: Faisal Masood Khanzada has nothing to disclose. Conflict of interest: Nasim Akhtar has nothing to disclose. Conflict of interest: Abdul Ghafoor has nothing to disclose. Conflict of interest: Alberto Trovato has nothing to disclose. Conflict of interest: Daniela Maria Cirillo has nothing to disclose. Conflict of interest: Sabira Tahseen has nothing to disclose.