Báez-Saldaña Renata, Delgado-Sánchez Guadalupe, García-García Lourdes, Cruz-Hervert Luis Pablo, Montesinos-Castillo Marlene, Ferreyra-Reyes Leticia, Bobadilla-Del-Valle Miriam, Canizales-Quintero Sergio, Ferreira-Guerrero Elizabeth, Téllez-Vázquez Norma, Montero-Campos Rogelio, Yanes-Lane Mercedes, Mongua-Rodriguez Norma, Martínez-Gamboa Rosa Areli, Sifuentes-Osornio José, Ponce-de-León Alfredo
Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México.
Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México.
PLoS One. 2016 Dec 28;11(12):e0168955. doi: 10.1371/journal.pone.0168955. eCollection 2016.
Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated.
To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico.
We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality.
Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables.
The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings.
异烟肼单耐药（IMR）是最常见的单耐药形式；据估计，其全球患病率在0.0%至9.5%之间。对于如何治疗这些患者尚无共识。
描述墨西哥韦拉克鲁斯州奥里萨巴市在项目条件下接受治疗的肺结核患者中，IMR结核病（TB）对治疗结局和生存的影响。
我们对墨西哥南部的肺结核患者进行了一项前瞻性队列研究。1995年至2010年期间，痰标本中抗酸杆菌或经培养证实为结核分枝杆菌的患者接受了流行病学、临床和微生物学评估。我们纳入了携带异烟肼单耐药（IMR）菌株的患者以及对异烟肼、利福平、乙胺丁醇和链霉素敏感的菌株患者。所有患者均按照墨西哥结核病项目指南进行治疗。我们进行年度随访以确定治疗结局、复发、再发和死亡率。
1995年至2010年期间，招募了1243例肺结核患者；902/1243（72.57%）进行了药敏试验；716例（79.38%）携带全敏感菌株，88例（9.75%）携带IMR菌株。与结核病患者有任何接触（调整优势比（aOR）1.85，95%置信区间（CI）1.15 - 2.96）和无家可归（调整优势比（aOR）2.76，95%CI 1.08 - 6.99）与IMR相关。IMR患者在HIV阴性患者中治疗失败的概率更高（调整风险比（HR）12.35，95%CI 3.38 - 45.15）以及因结核病死亡的概率更高（aHR 3.30，95%CI 1.00 - 10.84）。所有模型均针对社会人口学和临床变量进行了调整。
我们研究结果提供的证据表明，在新发病例和既往治疗过的肺结核及IMR患者中，使用一线药物的标准化治疗方案导致因结核病治疗失败和死亡的频率较高。我们建议重新评估携带IMR患者的最佳治疗方案。有必要加强科学研究，以评估类似环境下替代治疗方案。
