ORIGINAL RESEARCH article
Front. Tuberc.
Sec. Epidemiology of Tuberculosis
Volume 3 - 2025 | doi: 10.3389/ftubr.2025.1667354
Country-level Heterogeneity in MDR-TB Drug Susceptibility Supports Country-Specific Policy Development
Provisionally accepted
- 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom
- 2University College London Centre for Clinical Microbiology, London, United Kingdom
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Objectives The global challenge of tuberculosis (TB) is exacerbated by multidrug-resistant TB (MDR/RR-TB), confounded by country-level differences in TB prevention and care. The impact of local differences in drug-resistance selection pressure and transmission may be observed by analysing distributions of minimum inhibitory concentrations (MICs). Using the Bedaquiline Drug-Resistance Emergence Assessment in MDR-TB (DREAM) dataset, we analysed MIC distributions derived from a standard protocol across eleven countries and twelve antibiotics to explore country-level variation in drug susceptibility. Methods We analysed 71,135 MICs from 5,928 MDR/RR-TB isolates sampled from bedaquiline-naive patients. We compared MIC distributions across countries and WHO resistance classes, then used Spearman rank correlations to compare the drug-susceptibility within individual isolates by country. To explore the effect of bedaquiline use on resistance, we used linear regression to compare bedaquiline MICs with WHO data on bedaquiline usage. Results MIC distributions between countries were heterogeneous, especially for fluoroquinolones and isoniazid. The correlation analysis revealed a relationship between bedaquiline and clofazimine MICs in six countries. Analysis of isolates by resistance class demonstrated that XDR-TB isolates had higher MICs than MDR-TB isolates for antibiotics not part of the XDR definition. We found limited evidence to suggest that past bedaquiline usage at the national level led to raised bedaquiline MICs in patients not exposed to the drug. Conclusions Our research shows clear variations in drug susceptibility within M. tuberculosis across different countries and resistance classes, providing evidence of distinct drug-susceptibility dynamics per country. This expands the evidence for MDR-TB country differences and supports further country-specific policy development.
Keywords: bedaquiline drug susceptibility, Multidrug-resistant tuberculosis, Phenotypic drug resistance, minimum inhibitory concentrations, country variability, MIC distribution analysis, resistance surveillance data
Received: 16 Jul 2025; Accepted: 01 Sep 2025.
Copyright: © 2025 Fuller, Davies, McHugh and Knight. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Naomi M. Fuller, naomi.fuller@lshtm.ac.uk
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