International Union Against Tuberculosis and Lung Disease, Paris, France; Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Division of Pulmonary Medicine, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.
Indian J Tuberc. 2020 Dec;67(4S):S16-S22. doi: 10.1016/j.ijtb.2020.11.010. Epub 2020 Nov 28.
National tuberculosis programmes (NTPs) should aim for achieving a very high proportion of cure of all tuberculosis (TB) cases. Ineffective chemotherapy of TB that keeps a substantial proportion of patients alive without cure may amplify resistance during treatment and promote transmission of TB. In 2017, the World Health Organization (WHO) recommended that in patients who require TB retreatment, the retreatment regimen that comprised 8 months of isoniazid, rifampicin and ethambutol supplemented by streptomycin for the initial 2 months, and pyrazinamide for the initial 3 months (2SHRZE/HRZE/5HRE) should no longer be prescribed and drug susceptibility testing (DST) should be conducted to inform the choice of treatment regimen. While GeneXpert MTB/RIF assay may detect rifampicin resistance, it does not detect isoniazid resistance. A 6-month regimen consisting of rifampicin, isoniazid, pyrazinamide and ethambutol may be used for the treatment of previously treated cases in whom rifampicin resistance has been excluded but DST of isoniazid is not available. WHO recommended to treat isoniazid-resistant, rifampicin-susceptible TB (Hr-TB) with rifampicin, ethambutol, pyrazinamide and levofloxacin for a duration of 6 months. In several low- and middle-income countries, the majority of Hr-TB cases are detected after the initiation of treatment with first-line regimens. If patients have an unsatisfactory response to first-line treatment with persistent positive sputum, modification of regimens needs to be done very carefully. Adding a fluoroquinolone in cases with undetected rifampicin resistance runs the risk of acquired fluoroquinolone resistance. Recently, WHO advises NTPs to phase out the injectable-containing short regimen for multidrug-resistant and rifampicin-resistant TB (MDR-/RR-TB) and recommends that the preferred treatment option is a shorter, all-oral, bedaquiline-containing regimen. WHO emphasizes that access to rapid DST, especially for ruling out fluoroquinolone resistance, is required before starting the bedaquiline-containing shorter regimen. The problem is that access to rapid DST for ruling out fluoroquinolone resistance is limited in low- and middle-income countries. The use of WHO-recommended bedaquiline-containing regimens in the treatment of MDR-/RR-TB patients with undetected resistance to fluoroquinolones runs a high risk of acquired bedaquiline resistance, especially in settings with a high prevalence of fluoroquinolone resistance. It is crucial to mitigate the risks of both primary and acquired resistance of rifampicin, fluoroquinolone and bedaquiline by rational design of regimens and effective management of TB patients.
国家结核病规划（NTP）应致力于实现治愈所有结核病（TB）病例的极高比例。对结核病进行无效化疗，使相当一部分患者无法治愈而存活，可能会在治疗过程中放大耐药性，并促进结核病的传播。2017 年，世界卫生组织（WHO）建议，在需要复治的患者中，不再使用包含异烟肼、利福平、乙胺丁醇加链霉素（前 2 个月）和吡嗪酰胺（前 3 个月）的 8 个月复治方案（2SHRZE/HRZE/5HRE），应进行药物敏感性测试（DST）以指导治疗方案的选择。虽然 GeneXpert MTB/RIF 检测可以检测利福平耐药性，但不能检测异烟肼耐药性。对于已排除利福平耐药性但无法进行异烟肼 DST 的既往治疗病例，可以使用包含利福平、异烟肼、吡嗪酰胺和乙胺丁醇的 6 个月方案进行治疗。WHO 建议使用利福平、乙胺丁醇、吡嗪酰胺和左氧氟沙星治疗异烟肼耐药、利福平敏感的结核病（Hr-TB），疗程为 6 个月。在一些中低收入国家，大多数 Hr-TB 病例是在一线方案治疗开始后发现的。如果患者对一线治疗反应不佳，持续痰阳性，需要非常小心地修改方案。在未检出利福平耐药的情况下，添加氟喹诺酮类药物可能会导致获得性氟喹诺酮耐药性。最近，世卫组织建议国家结核病规划逐步淘汰含有注射剂的短程方案，用于耐多药和利福平耐药结核病（MDR-/RR-TB），并建议首选的治疗方案是更短的、全口服、包含贝达喹啉的方案。世卫组织强调，在开始使用包含贝达喹啉的较短方案之前，需要获得快速药物敏感性检测（DST），特别是排除氟喹诺酮耐药性。问题是，在中低收入国家，获得快速 DST 以排除氟喹诺酮耐药性的机会有限。在未检出对氟喹诺酮类药物耐药的 MDR-/RR-TB 患者中使用世卫组织推荐的包含贝达喹啉的方案，会极大地增加获得贝达喹啉耐药性的风险，尤其是在氟喹诺酮类药物耐药率较高的环境中。通过合理设计方案和有效管理结核病患者，减轻利福平、氟喹诺酮类药物和贝达喹啉的原发性和获得性耐药风险至关重要。
