Hospital Nacional Arzobispo Loayza, Lima, Perú.
Dirección de Prevención y Control de Tuberculosis, Ministry of Health, Lima, Peru.
PLoS One. 2018 Dec 4;13(12):e0206658. doi: 10.1371/journal.pone.0206658. eCollection 2018.
Resistance to isoniazid is the most common form of drug-resistance in tuberculosis. However only a tiny proportion of TB patients in the world have access to isoniazid drug susceptibility testing-the widely implemented Xpert MTB/RIF technology only tests for resistance to rifampicin. Patients with isoniazid mono resistance that is not identified at baseline are treated with a standard regimen that effectively results in rifampicin mono-therapy during the latter four months of the six month treatment course, exposing remaining viable organisms to a single agent and greatly increasing the risk of development of multi drug-resistant TB. Unusually, Peru has pioneered universal pre-treatment drug susceptibility testing with methods that identify isoniazid resistance and has thus identified a large number of individuals requiring tailored therapy. Since 2010, treatment in Peru for isoniazid-resistant tuberculosis without multidrug-resistant tuberculosis (Hr-TB) has been with a standardized nine-month regimen of levofloxacin, rifampicin, ethambutol and pyrazinamide. The objectives of this study were to evaluate the outcomes of treatment for patients with Hr-TB initiating treatment with this regimen between January 2012 and December 2014 and to determine factors affecting these outcomes.
Retrospective cross-sectional study; case data were obtained from the national registry of drug-resistant tuberculosis. Patients diagnosed with isoniazid resistant TB without resistance to rifampicin, pyrazinamide, ethambutol and quinolones as determined by either a rapid drug susceptibility testing (DST) (nitrate reductase test, MODS, Genotype MTBDRplus) or by the proportion method were included.
A total of 947 cases were evaluated (a further 403 without treatment end date were excluded), with treatment success in 77.2% (731 cases), loss to follow-up in 19.7% (186 cases), treatment failure in 1.2% (12 cases), and death in 1.9% (18 cases). Unfavorable outcomes were associated in multivariate analysis with male gender (OR 0.50, 95% CI 0.34-0.72, p<0.05), lack of rapid DST (OR 0.67, 95% CI 0.50-0.91, p = 0.01), additional use of an injectable second-line anti-tuberculous drug (OR 0.46, 95% CI 0.31-0.70, p<0.05), and treatment initiation in 2014 (OR 0.77, 95% CI 0.62-0.94, p = 0.01).
The treatment regimen implemented in Peru for isoniazid resistant TB is effective for TB cure and is not improved by addition of an injectable second-line agent. Access to rapid DST and treatment adherence need to be strengthened to increase favorable results.
对异烟肼的耐药性是结核病中最常见的耐药形式。然而，世界上只有一小部分结核病患者能够进行异烟肼药物敏感性测试——广泛实施的 Xpert MTB/RIF 技术仅检测对利福平的耐药性。基线时未发现异烟肼单耐药的患者接受标准方案治疗，在 6 个月疗程的后四个月期间实际上有效地导致利福平单治疗，使剩余存活的病原体暴露于单一药物下，大大增加了发展为耐多药结核病的风险。秘鲁不同寻常的是，它率先采用了普遍的治疗前药物敏感性测试方法，该方法可以识别异烟肼耐药性，并因此发现了大量需要个体化治疗的患者。自 2010 年以来，秘鲁对无耐多药结核病（Hr-TB）的异烟肼耐药结核病的治疗一直采用标准化的 9 个月左氧氟沙星、利福平、乙胺丁醇和吡嗪酰胺方案。本研究的目的是评估 2012 年 1 月至 2014 年 12 月期间采用该方案治疗 Hr-TB 患者的治疗结果，并确定影响这些结果的因素。
回顾性横断面研究；病例数据来自国家耐药结核病登记处。纳入标准为通过快速药物敏感性测试（DST）（硝酸盐还原酶试验、MODS、基因型 MTBDRplus）或比例法确定的耐异烟肼但对利福平、吡嗪酰胺、乙胺丁醇和喹诺酮类药物无耐药性的患者。
共评估了 947 例病例（另有 403 例无治疗结束日期的病例被排除），其中 77.2%（731 例）治疗成功，19.7%（186 例）失访，1.2%（12 例）治疗失败，1.9%（18 例）死亡。多因素分析显示，男性（OR 0.50，95%CI 0.34-0.72，p<0.05）、缺乏快速 DST（OR 0.67，95%CI 0.50-0.91，p=0.01）、额外使用注射用二线抗结核药物（OR 0.46，95%CI 0.31-0.70，p<0.05）和 2014 年开始治疗（OR 0.77，95%CI 0.62-0.94，p=0.01）与不良结局相关。
秘鲁实施的治疗耐异烟肼结核病的方案对结核病治愈有效，且添加注射用二线药物并不能提高疗效。需要加强快速 DST 的获取和治疗依从性，以提高治疗效果。
