New drugs to treat difficult tuberculous and nontuberculous mycobacterial pulmonary disease

Purpose of review Treatment of drug-sensitive tuberculosis (TB) is effective, whereas that of multidrug-resistant and extensively drug-resistant TB as well as nontuberculous mycobacterial (NTM) disease are less so. Therapy in general requires good adherence to potentially toxic drug regimens over prolonged periods. Poor adherence is associated with resistance development and poor outcome. This review will present promising new treatments, both new drugs and regimens, for difficult mycobacterial pulmonary infections. Recent findings A number of new and repurposed drugs including bedaquiline, delamanid, pretomanid, linezolid and clofazimine, and drug regimens, such as the STREAM trial regimens, are currently progressing from basic research through clinical trials. Summary (1) The role of bedaquiline and delamanid in TB and NTM treatment is still not clearly defined. (2) New and repurposed drugs such as pretomanid, linezolid and clofazimine have the potential to advance TB and NTM treatment. Inhaled liposomal amikacin shows promise in pulmonary NTM disease. (3) Patients with multidrug-resistant TB, extensively drug-resistant TB and NTM disease should be offered the choice to participate in drug trials that may shorten or otherwise improve their experience of treatment. (4) The use of an effective regimen based on appropriate NTM-specific drug susceptibility testing should be a cornerstone of treatment for NTM as much as it is for Mycobacterium tuberculosis treatment. (5) All new drugs identified for Mycobacterium tuberculosis should also be tested for activity against NTM, though robust tools for NTM drug susceptibility testing are required.