抗结核药物及其耐药相关突变位点的研究进展

结核病是结核分枝杆菌复合物引起的传染性疾病,致死率、致残率高,在全球传染病中居第2位。近年来耐药结核病所占比例逐年升高,成为消灭结核病面临的巨大挑战之一。传统的耐药诊断方法基于培养,费时费力,所需技术要求高;而现有分子检测方法仅能检测少量抗结核药物的少数耐药基因。因此,更好地理解抗结核药物的耐药机制有助于全面耐药诊断。本文对临床中使用频率较高的11类一线和二线抗结核药物及其相应耐药相关基因、突变位点的研究进展进行总结,尤其是对环丝氨酸、利奈唑胺、氯法齐明等二线药物的近期研究做了系统描述,为全面耐药诊断、精准治疗指导、新药研发及耐药机制深入研究提供了前期工作基础。

Advances in research on anti-tuberculosis drugs and resistance-related mutations

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis complex, and the mortality rate is the second highest among the infectious diseases worldwide. The increasing proportion of drug-resistant tuberculosis has become one of the great challenges in eradicating tuberculosis. The traditional diagnosis method of drug resistance is based on culture, which takes time, effort and high technical requirements. Existing molecular detection methods can only detect a small number of anti-tuberculosis drug resistance genes, so a better understanding of anti-tuberculosis drug resistance mechanisms will contribute to a comprehensive resistance diagnosis. This article summarizes the research progress on eleven first- and second-line anti-tuberculosis drugs and their corresponding drug resistance-related genes and mutation sites. Recent studies on second-line drugs such as cycloserine, linezolid, and clofazimine have been systematically described, providing a preliminary basis for the study of comprehensive drug resistance diagnosis, accurate guidance for treatment, research and development of new drugs, and in-depth drug resistance mechanisms.