Mortality risks in multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis: a systematic review and meta-regression analysis

Abstract

Tuberculosis (TB) remains a leading cause of infectious disease mortality globally, and the emergence ofdrug-resistant strains poses a significant threat to TB control efforts. This study aimed to quantify the relative mortality risks associated with multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), in comparison to drug-susceptible TB (DS-TB) and MDR-TB, respectively. A systematic review was conducted following PRISMA guidelines, and eligible studies reporting comparative mortality outcomes were identified through PubMed, Embase, and Global Health databases. A total of 62 studies were included in the meta-analysis. Random-effects models were used to pool relative risk estimates, and meta-regression analyses were conducted to explore the influence of contextual moderators such as country income group, HIV status, and urbanicity. Results showed that MDR-TB was associated with significantly higher mortality compared to DS-TB, particularly in low-income countries and among populations exclusively living with HIV. For XDR-TB versus MDR-TB, urbanicity emerged as a significant moderator, with higher mortality observed in urban settings. XDR-TB exhibited consistently elevated mortality across most contexts, indicating the limited moderating effect of structural variables beyond urbanicity. These findings highlight the disproportionate impact of drug resistance on vulnerable populations and underscore the urgency of expanding diagnostic and treatment capacity in high-burden, low-resource, and urban settings. This work contributes to the global evidence base supporting more equitable TB control strategies and context-specific public health interventions.