Abstract
BACKGROUND: Strains of Mycobacterium tuberculosis with resistance to the new and repurposed drugs included in the all-oral shorter TB regimens recommended by WHO for the treatment of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) are becoming increasingly common globally. When strains of M. tuberculosis have resistance to one or more of these drugs (bedaquiline, linezolid, third-generation fluoroquinolones, delamanid, pretomanid, or clofazimine), they are more challenging to treat. METHODS: In the absence of trial data on how to care for these individuals, a group of clinical, programmatic and civil society experts came together to generate a series of best clinical practices. These practices are based on the published literature and on experience caring for individuals with these forms of TB. RESULTS: We discuss best clinical practices in the following areas: 1) drug susceptibility testing; 2) regimen design; 3) adverse event monitoring and management; 4) special populations; 5) shared decision making and informed consent; 6) holistic packages of support; and 7) pre-approval access/compassionate use of newer TB compounds. CONCLUSION: While we await systematic studies of treatment approaches to generate the necessary evidence base, the clinical practices described here can be used to guide the programmatic care of people with strains of M. tuberculosis that have expanded resistance.