Effectiveness and Safety of Contemporary Drug Regimens for Multidrug- and Extensively Drug-resistant Tuberculosis in Children and Adolescents: A Global Systematic Review and Meta-analysis

Background Children and adolescents with multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis (TB) face major treatment challenges. Although newer all-oral regimens have transformed adult TB care, their use in younger populations has largely been extrapolated from adult studies, despite important biologic and clinical differences. Systematic and up-to-date evidence on the effectiveness and safety of contemporary regimens in children and adolescents is lacking. We conducted a global systematic review and meta-analysis to address this gap. Methods We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library and Google Scholar for studies published between January 1, 2015, and September 1, 2025. Eligible studies included children 0-19 years old with confirmed or presumed MDR/XDR-TB or rifampicin-TB receiving pharmacologic treatment. Outcomes were pooled using a random-effects meta-analysis. The primary outcome was treatment success (cure or completion); severe (grade 3/4) adverse events were assessed as secondary outcomes. Results We included 14 studies comprising 490 children across 13 countries. Overall pooled treatment success was 89% (95% confidence interval: 84%-93%; I2 = 51.9%). Newer all-oral regimens achieved slightly higher success (91%) than injectable-containing regimens (83%). Severe grade 3/4 adverse event were sparse (7 of 14 studies); events occurred in 21% (95% confidence interval: 13%-33%), most commonly QT prolongation and anemia, with limited specific drug attribution. Conclusions Newer, all-oral bedaquiline- and delamanid-based regimens for pediatric MDR/XDR-TB are effective and generally well tolerated, though the full safety profile remains incompletely characterized. In pediatric MDR/XDR-TB, where studies are rare, our findings provide the best available evidence and a foundation for improved treatment guidelines and future research.