1. Whole-genome sequencing drug susceptibility testing is associated with positive MDR-TB treatment response.
- Author
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Larsson L, Corbett C, Kalmambetova G, Utpatel C, Ahmedov S, Antonenka U, Iskakova A, Kadyrov A, Kohl TA, Barilar V, Sahalchyk E, Niemann S, Hoffmann H, and Kranzer K
- Subjects
- Humans, Female, Male, Adult, Young Adult, Middle Aged, Kyrgyzstan, Cohort Studies, Treatment Outcome, Logistic Models, Adolescent, Tuberculosis, Multidrug-Resistant drug therapy, Tuberculosis, Multidrug-Resistant microbiology, Whole Genome Sequencing, Antitubercular Agents pharmacology, Microbial Sensitivity Tests, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis isolation & purification, Rifampin pharmacology, Rifampin therapeutic use
- Abstract
BACKGROUND Until recently, multidrug-resistant TB (MDR-TB) was treated with lengthy and toxic regimens. New three-drug anti-TB regimens raise the question of whether they are sufficiently active for MDR-TB in Central Asia, an MDR-TB hotspot region.METHODS In a cohort of rifampicin-resistant (RR) and MDR-TB patients in the Kyrgyz Republic, we investigated the impact of the number of drugs that were tested susceptible by whole-genome sequencing (WGS) and conventional drug susceptibility testing (DST) and used for treatment on the treatment response, defined as 'matches'. Logistic regressions were performed to assess the effect of having ≥ 4 susceptible drugs in a regimen at baseline and at Month 2 on the treatment response.RESULTS The study included 227 participants with RR/MDR-TB (30.8% female; median age 30.4 years). The age- and sex-adjusted analysis showed an association between a regimen with ≥ 4 WGS matches at baseline (adjusted odds ratio [aOR] 2.10, 95% CI 1.00-4.41). No association was found when using conventional DST to define matches. .CONCLUSION Our study confirms that the inclusion of four efficacious anti-TB drugs in an MDR-TB regimen increases the chances of a positive treatment response. Susceptibility of at least four drugs in WGS-DST predicts a positive treatment response.- Published
- 2024
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