Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA.
Nat Rev Microbiol. 2024 Oct;22(10):617-635. doi: 10.1038/s41579-024-01025-1. Epub 2024 Mar 22.
Drug-resistant tuberculosis (TB) is estimated to cause 13% of all antimicrobial resistance-attributable deaths worldwide and is driven by both ongoing resistance acquisition and person-to-person transmission. Poor outcomes are exacerbated by late diagnosis and inadequate access to effective treatment. Advances in rapid molecular testing have recently improved the diagnosis of TB and drug resistance. Next-generation sequencing of Mycobacterium tuberculosis has increased our understanding of genetic resistance mechanisms and can now detect mutations associated with resistance phenotypes. All-oral, shorter drug regimens that can achieve high cure rates of drug-resistant TB within 6-9 months are now available and recommended but have yet to be scaled to global clinical use. Promising regimens for the prevention of drug-resistant TB among high-risk contacts are supported by early clinical trial data but final results are pending. A person-centred approach is crucial in managing drug-resistant TB to reduce the risk of poor treatment outcomes, side effects, stigma and mental health burden associated with the diagnosis. In this Review, we describe current surveillance of drug-resistant TB and the causes, risk factors and determinants of drug resistance as well as the stigma and mental health considerations associated with it. We discuss recent advances in diagnostics and drug-susceptibility testing and outline the progress in developing better treatment and preventive therapies.
耐多药结核病（TB）估计导致全球所有与抗菌药物耐药性相关死亡的 13%，由持续获得耐药性和人与人之间的传播所驱动。诊断延迟和无法获得有效治疗加剧了不良预后。快速分子检测技术的进步最近改善了结核病和耐药性的诊断。结核分枝杆菌的下一代测序增加了我们对遗传耐药机制的理解，现在可以检测与耐药表型相关的突变。目前有全口服、较短疗程的药物方案，可在 6-9 个月内实现高治愈率的耐多药结核病，但尚未在全球临床应用中推广。有前景的预防高危接触者耐多药结核病的方案得到了早期临床试验数据的支持，但最终结果仍有待确定。以患者为中心的方法对于耐多药结核病的管理至关重要，可降低不良治疗结果、副作用、与诊断相关的耻辱感和心理健康负担的风险。在这篇综述中，我们描述了耐多药结核病的当前监测以及耐药性的原因、风险因素和决定因素，以及与耐药性相关的耻辱感和心理健康问题。我们讨论了诊断和药敏试验的最新进展，并概述了开发更好的治疗和预防疗法的进展。
