Recent advances in the treatment of tuberculosis.

BACKGROUND Tuberculosis is a global health challenge and one of the leading causes of death worldwide. In the last decade, the tuberculosis treatment landscape has dramatically changed. After long years of stagnation, new compounds entered the market (bedaquiline, delamanid and pretomanid) and phase III clinical trials have shown promising results towards shortening duration of treatment for both drug-susceptible (Study 31/A5349, TRUNCATE-TB, SHINE) and drug-resistant tuberculosis (STREAM, NiX-TB, ZeNix, TB-PRACTECAL). Dose optimization of rifamycins and repurposed drugs have also brought hopes of further development of safe and effective regimens. Consequently, international and World Health Organization clinical guidelines have been updated multiple times in the last years to keep pace with these advances. OBJECTIVES This narrative review aims to summarize the state-of-the-art on treatment of drug-susceptible and drug-resistant tuberculosis, as well as recent trials results and an overview of ongoing clinical trials. SOURCES A non-systematic literature review was conducted in PubMed and MEDLINE, focusing on the treatment of tuberculosis. Ongoing clinical trials were listed according to the authors' knowledge, and completed consulting clinicaltrials.gov and other publicly available websites (www.resisttb.org/clinical-trials-progress-report, www.newtbdrugs.org/pipeline/trials). CONTENT This review summarizes the recent, major changes in the landscape for drug-susceptible and drug-resistant treatment, with a specific focus on their potential impact on patient outcomes and programmatic TB management. Moreover, insights in host-directed therapies, and advances in pharmacokinetic and pharmacogenomics are discussed. A thorough outline of ongoing therapeutic clinical trials is presented, highlighting different approaches and goals in current TB clinical research. IMPLICATIONS Future research should be directed to individualize regimens and protect these recent breakthroughs by preventing and identifying the selection of drug resistance and providing widespread, affordable, patient-centered access to new treatment options for all people affected by tuberculosis