Villegas Leonela, Otero Larissa, Sterling Timothy R, Huaman Moises A, Van der Stuyft Patrick, Gotuzzo Eduardo, Seas Carlos
Vanderbilt University School of Medicine, Nashville, TN, United States of America.
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru.
PLoS One. 2016 Apr 5;11(4):e0152933. doi: 10.1371/journal.pone.0152933. eCollection 2016.
Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB) treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes.
A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ) media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment.
Of 1292 patients enrolled, 1039 (80%) were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8%) patients and rifampicin mono-resistance was present in 24 (2%) patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR) = 2.10; 95% confidence interval (CI): 1.1-4.1), and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9-47.8). Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01) and death (4/85, 5%, p<0.02). Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01).
A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes.
异烟肼和利福平是治疗结核病（TB）最有效的两种一线药物。我们评估了异烟肼和利福平单药耐药的患病率、相关危险因素以及单药耐药与治疗结果的关联。
一项前瞻性观察队列研究纳入了2010年3月至2011年12月期间来自秘鲁利马北部一个地区34个卫生机构的初发涂片阳性肺结核成年患者。对参与者进行访谈，并在罗-琴（LJ）培养基上培养痰样本。采用比例法进行药敏试验。记录每位患者的用药方案。我们的主要结局是治疗结束时的治疗结果。次要结局包括治愈患者在完成治疗后两年内的复发情况。
在1292名入组患者中，1039名（80%）培养结果为阳性。在这个亚组中，85名（8%）患者存在异烟肼单药耐药，24名（2%）患者存在利福平单药耐药。在多因素逻辑回归模型中，异烟肼单药耐药与非法药物使用相关（调整后的比值比（aOR）=2.10；95%置信区间（CI）：1.1 - 4.1），利福平单药耐药与HIV感染相关（aOR = 9.43；95%CI：1.9 - 47.8）。异烟肼单药耐药患者出现包括治疗失败（2/85，2%，p值<0.01）和死亡（4/85，5%，p<0.02）在内的不良治疗结果的风险更高。利福平单药耐药患者的死亡风险更高（2/24，8%，p<0.01）。
在我们这个低HIV负担地区的结核病患者中，异烟肼和利福平单药耐药的患病率较高，这与高HIV负担地区相似。异烟肼和利福平单药耐药患者出现不良治疗结果的风险增加。
