Delamanid and Pretomanid: From Bench to Bedside

Tuberculosis (TB) stemming from Mycobacterium tuberculosis (Mtb) continues to pose a formidable global health challenge, claiming numerous lives annually. Despite progress in treatment, the emergence of drug-resistant strains, including multidrugresistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), poses challenges to effective management, thus necessitating the development of novel medications. Nitroimidazoles, exemplified by delamanid and pretomanid, have emerged as promising candidates in the battle against TB. Their multifaceted mechanisms of action encompass interference with mycolic acid synthesis in aerobic conditions and respiratory poisoning in anaerobic environments, rendering them effective against both actively replicating and dormant mycobacteria. Despite their potential, concerns surrounding the emergence of drug resistance underscore the need for judicious utilization and vigilant monitoring. Delamanid, indicated for rifampicin-resistant and MDR-TB, and pretomanid, integrated into multidrug regimens for extensively drug-resistant and MDR-TB, signify critical milestones in addressing drug-resistant TB. These advances are aligned with the global endeavor to achieve TB-related Sustainable Development Goals by 2030, offering renewed hope for diminishing TB’s impact on public health. This chapter sheds light on the journey of delamanid and pretomanid, the challenges faced during their development, and sets a benchmark for future drug discovery against MDR and XDR TB.