Whole-genome sequencing drug susceptibility testing is associated with positive MDR-TB treatment response

• Published in: The international journal of tuberculosis and lung disease 2024-10, Vol.28 (10), p.494-499
• Main Authors: Larsson, L., Corbett, C., Kalmambetova, G., Utpatel, C., Ahmedov, S., Antonenka, U., Iskakova, A., Kadyrov, A., Kohl, T.A., Barilar, V., Sahalchyk, E., Niemann, S., Hoffmann, H., Kranzer, K.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antitubercular Agents - pharmacology; Cohort Studies; Drug Resistance; Drugs; Dst; Female; Gene sequencing; Genomes; Humans; Kyrgyzstan; Logistic Models; Male; Microbial Sensitivity Tests; Middle Aged; Multidrug resistance; Multidrug-Resistant Tb; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Rifampin; Rifampin - pharmacology; Rifampin - therapeutic use; Sex ratio; Treatment Outcome; Tuberculosis; Tuberculosis, Multidrug-Resistant - drug therapy; Tuberculosis, Multidrug-Resistant - microbiology; Wgs; Whole Genome Sequencing; Young Adult
• ISSN: 1027-3719; 1815-7920; 1815-7920
• DOI: 10.5588/ijtld.24.0052

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.