Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Summary

This IPD meta-analysis (42 studies; 23,369 participants) found that inclusion of two or three WHO Group A drugs (bedaquiline, a fluoroquinolone, linezolid) was independently associated with higher treatment success in children/adolescents with MDR/RR-TB. Overall pediatric outcomes were better than adults but still below global targets, underscoring the need to expand access and optimize regimens.

Key Findings

• Across 23,369 pediatric MDR/RR-TB cases, overall treatment success was 72.0%, death 12.2%, failure 3.1%, loss to follow-up 12.7%.
• Use of two Group A drugs increased odds of success (adjusted OR 1.41), and three Group A drugs further increased success (adjusted OR 2.12).
• Younger and clinically diagnosed children were underrepresented among those treated, indicating case-finding gaps.

Clinical Implications

Prioritize inclusion of ≥2 Group A drugs when constructing pediatric MDR/RR-TB regimens and accelerate access to bedaquiline, linezolid, and fluoroquinolones. Strengthen case-finding among younger and clinically diagnosed children who are underrepresented in treated cohorts.

Limitations

• Heterogeneity of observational cohorts and regimens across settings
• Loss to follow-up (12.7%) may bias outcome estimates

Future Directions

Prospective pragmatic trials optimizing Group A backbones in pediatric MDR/RR-TB, including safety/PK in younger age groups; implementation studies to expand drug access.