基岩
氯法齐明
肺结核
医学
吡嗪酰胺
背景(考古学)
重症监护医学
抗药性
分子诊断学
药物开发
药品
GeneXpert MTB/RIF公司
结核分枝杆菌
药理学
生物信息学
生物
免疫学
病理
遗传学
古生物学
麻风病
作者
Sophia B. Georghiou,Margaretha de Vos,Kavindhran Velen,Paolo Miotto,Rebecca E. Colman,Daniela María Cirillo,Nazir Ismail,Timothy C. Rodwell,Anita Suresh,Morten Rühwald
标识
DOI:10.1080/22221751.2023.2178243
摘要
Diagnostic development must occur in parallel with drug development to ensure the longevity of new treatment compounds. Despite an increasing number of novel and repurposed anti-tuberculosis compounds and regimens, there remains a large number of drugs for which no rapid and accurate molecular diagnostic option exists. The lack of rapid drug susceptibility testing for linezolid, bedaquiline, clofazimine, the nitroimidazoles (i.e pretomanid and delamanid) and pyrazinamide at any level of the healthcare system compromises the effectiveness of current tuberculosis and drug-resistant tuberculosis treatment regimens. In the context of current WHO tuberculosis treatment guidelines as well as promising new regimens, we identify the key diagnostic gaps for initial and follow-on tests to diagnose emerging drug resistance and aid in regimen selection. Additionally, we comment on potential gene targets for inclusion in rapid molecular drug susceptibility assays and sequencing assays for novel and repurposed drug compounds currently prioritized in current regimens, and evaluate the feasibility of mutation detection given the design of existing technologies. Based on current knowledge, we also propose design priorities for next generation molecular assays to support triage of tuberculosis patients to appropriate and effective treatment regimens. We encourage assay developers to prioritize development of these key molecular assays and support the continued evolution, uptake, and utility of sequencing to build knowledge of tuberculosis resistance mechanisms and further inform rapid treatment decisions in order to curb resistance to critical drugs in current regimens and achieve End TB targets.Trial registration: ClinicalTrials.gov identifier: NCT05117788..
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