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

IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES
L Larsson, C Corbett, G Kalmambetova, C Utpatel, S Ahmedov, U Antonenka, A Iskakova, A Kadyrov, T A Kohl, V Barilar, E Sahalchyk, S Niemann, H Hoffmann, K Kranzer
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Abstract

BACKGROUNDUntil 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.METHODSIn 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.RESULTSThe 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.CONCLUSIONOur 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..

全基因组测序药物敏感性检测与阳性 MDR-TB 治疗反应相关。
背景直到最近,耐多药结核病(MDR-TB)的治疗一直采用漫长而有毒的治疗方案。在吉尔吉斯共和国的一组耐利福平(RR)和 MDR-TB 患者中,我们研究了通过全基因组测序(WGS)和传统药物敏感性检测(DST)检测出的药物敏感性并用于治疗的药物数量对治疗反应(定义为 "匹配")的影响。结果研究纳入了 227 名 RR/MDR-TB 患者(30.8% 为女性;中位年龄 30.4 岁)。经年龄和性别调整后的分析表明,基线时有≥4个WGS匹配的治疗方案与治疗反应之间存在关联(调整赔率[aOR]2.10,95% CI 1.00-4.41)。结论我们的研究证实,在 MDR-TB 治疗方案中加入四种有效的抗结核药物可增加治疗反应阳性的几率。在 WGS-DST 中,至少四种药物的敏感性可预测阳性治疗反应。
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来源期刊
CiteScore
4.90
自引率
20.00%
发文量
266
审稿时长
2 months
期刊介绍: The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.
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