Multidrug-resistant tuberculosis in children: A practical update on epidemiology, diagnosis, treatment and prevention

Abstract

Pediatric multidrug-resistant tuberculosis (MDR-TB) remains a significant global problem, and there are numerous barriers preventing children with MDR-TB from being identified, confirmed with microbiologic tests, and treated with a safe, practical, and effective regimen. However, several recent advances in diagnostics and treatment regimens have the promise to improve outcomes for children with MDR-TB. We introduce this review with two cases that exemplify both the challenges in management of MDR-TB in children, but also the potential to achieve a positive outcome. More than 30,000 cases of MDR-TB per year are believed to occur in children but less than 5% are confirmed microbiologically, contributing to poorer outcomes and excess mortality. Rapid molecular-based testing that provides information on rifampin susceptibility is increasingly globally available and recommended for all children suspected of TB disease--but remains limited by challenges obtaining appropriate samples and the paucibacillary nature of most pediatric TB. More complex assays allowing better characterization of drug-resistant isolates are emerging. For children diagnosed with MDR-TB, treatment regimens have traditionally been long and utilize multiple drugs associated with significant side effects, particularly injectable agents. Several new or repurposed drugs including bedaquiline, delamanid, clofazimine and linezolid now allow most treatment regimens to be shorter and all-oral. Yet data to support short, all-oral, novel regimens for young children containing pretomanid remain insufficient at present, and there is a compelling need to conduct pediatric trials of promising therapeutics and MDR-TB treatment regimens.