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.