Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
Pharmacy Services, Alberta Health Services, Calgary, Alberta, Canada.
PLoS One. 2020 Mar 10;15(3):e0229691. doi: 10.1371/journal.pone.0229691. eCollection 2020.
Isoniazid resistant Mycobacterium tuberculosis (Hr-TB) is the most frequently encountered TB resistance phenotype in North America but limited data exist on the effectiveness of current therapeutic regimens. Ineffective treatment of Hr-TB increases patient relapse and anti-mycobacterial resistance, specifically MDR-TB. We undertook a multi-centre, retrospective review of culture-positive Hr-TB patients in Alberta, Canada (2007-2017). We assessed incidence and treatment outcomes, with a focus on fluoroquinolone (FQ)-containing regimens, to understand the risk of unsuccessful outcomes. Rates of Hr-TB were determined using the mid-year provincial population and odds of unsuccessful treatment was calculated using a Fisher's Exact test. One hundred eight patients of median age 37 years (IQR: 26-50) were identified with Hr-TB (6.3%), 98 of whom were able to be analyzed. Seven percent reported prior treatment. Rate of foreign birth was high (95%), but continent of origin did not predict Hr-TB (p = 0.47). Mean compliance was 95% with no difference between FQ and non-FQ regimens (p = 1.00). Treatment success was high (91.8%). FQ-containing regimens were frequently initiated (70%), with no difference in unsuccessful outcomes compared to non-FQ-containing regimens (5.8% vs. 13.8%, OR 0.4, 95% CI 0.1-2.3, p = 0.23). Only one patient (1%) utilizing a less common non-FQ-based regimen including two months of pyrazinamide developed secondary multidrug resistance. Unsuccessful treatment was low (<10%) relative to comparable literature (~15%) and showed similar outcomes for FQ and non-FQ-based regimens and no deficit to those using intermittent fluoroquinolones in the continuation phase of treatment. Our findings are similar to recent data, however prospective, randomized trials of adequate power are needed to determine the optimal treatment for Hr-TB.
耐异烟肼分枝杆菌(Hr-TB)是北美最常见的结核耐药表型,但目前关于现有治疗方案的疗效的数据有限。Hr-TB 治疗无效会增加患者复发和抗分枝杆菌耐药的风险,特别是耐多药结核(MDR-TB)。我们对加拿大艾伯塔省(2007-2017 年)的培养阳性 Hr-TB 患者进行了一项多中心回顾性研究。我们评估了发病率和治疗结果,重点关注含氟喹诺酮(FQ)的方案,以了解治疗失败的风险。采用年度中期省级人口计算 Hr-TB 发生率,采用 Fisher 精确检验计算治疗失败的可能性。共确定了 108 例中位年龄为 37 岁(IQR:26-50)的 Hr-TB 患者(6.3%),其中 98 例可进行分析。7%的患者报告有既往治疗史。高比例(95%)的患者有外国出生史,但原籍地并不能预测 Hr-TB(p = 0.47)。平均遵医嘱率为 95%,FQ 和非 FQ 方案之间无差异(p = 1.00)。治疗成功率高(91.8%)。经常开始使用含 FQ 的方案(70%),与非 FQ 方案相比,治疗失败率无差异(5.8%比 13.8%,OR 0.4,95%CI 0.1-2.3,p = 0.23)。只有 1 名(1%)患者使用了包括两个月吡嗪酰胺的不太常见的非 FQ 为基础的方案,发生了继发性耐多药。与类似的文献(~15%)相比,治疗失败率较低(<10%),且 FQ 和非 FQ 方案的治疗结果相似,在治疗的延续阶段间歇性使用氟喹诺酮也没有缺陷。我们的发现与最近的数据相似,但需要进行具有足够效力的前瞻性、随机试验,以确定 Hr-TB 的最佳治疗方法。