Pham Ngoc Thach Hospital, 120 Hung Vuong, Ho Chi Minh City, Vietnam.
Oxford University Clinical Research Unit, 763 Vo Van Kiet, Ho Chi Minh City, Vietnam.
BMC Infect Dis. 2018 Mar 6;18(1):112. doi: 10.1186/s12879-018-3033-9.
Drug resistant tuberculosis (TB) is increasing in prevalence worldwide. Treatment failure and relapse is known to be high for patients with isoniazid resistant TB treated with standard first line regimens. However, risk factors for unfavourable outcomes and the optimal treatment regimen for isoniazid resistant TB are unknown. This cohort study was conducted when Vietnam used the eight month first line treatment regimen and examined risk factors for failure/relapse among patients with isoniazid resistant TB.
Between December 2008 and June 2011 2090 consecutive HIV-negative adults (≥18 years of age) with new smear positive pulmonary TB presenting at participating district TB units in Ho Chi Minh City were recruited. Participants with isoniazid resistant TB identified by Microscopic Observation Drug Susceptibility (MODS) had extended follow-up for 2 years with mycobacterial culture to test for relapse. MGIT drug susceptibility testing confirmed 239 participants with isoniazid resistant, rifampicin susceptible TB. Bacterial and demographic factors were analysed for association with treatment failure and relapse.
Using only routine programmatic sputum smear microscopy for assessment, (months 2, 5 and 8) 30/239 (12.6%) had an unfavourable outcome by WHO criteria. Thirty-nine patients were additionally detected with unfavourable outcomes during 2 year follow up, giving a total of 69/239 (28.9%) of isoniazid (INH) resistant cases with unfavourable outcome by 2 years of follow-up. Beijing lineage was the only factor significantly associated with unfavourable outcome among INH-resistant TB cases during 2 years of follow-up. (adjusted OR = 3.16 [1.54-6.47], P = 0.002).
One third of isoniazid resistant TB cases suffered failure/relapse within 2 years under the old eight month regimen. Over half of these cases were not identified by standard WHO recommended treatment monitoring. Intensified research on early identification and optimal regimens for isoniazid resistant TB is needed. Infection with Beijing genotype of TB is a significant risk factor for bacterial persistence on treatment resulting in failure/relapse within 2 years. The underlying mechanism of increased tolerance for standard drug regimens in Beijing genotype strains remains unknown.
全球范围内，耐多药结核病（TB）的患病率呈上升趋势。采用标准一线方案治疗耐异烟肼结核病的患者，其治疗失败和复发率已知较高。然而，耐异烟肼结核病患者不良结局的危险因素以及最佳治疗方案尚不清楚。本队列研究在越南采用 8 个月一线治疗方案时进行，旨在研究耐异烟肼结核病患者的失败/复发的危险因素。
2008 年 12 月至 2011 年 6 月，胡志明市参与区结核病单位收治了 2090 例连续的 HIV 阴性成人（≥18 岁），他们均为新出现的痰涂片阳性肺结核患者。采用微量全自动化药物敏感性检测法（MGIT）药敏试验对耐异烟肼的患者进行确认，并对他们进行了 2 年的扩展随访，进行分枝杆菌培养以检测复发。MGIT 药物敏感性检测证实了 239 例耐异烟肼、利福平敏感的肺结核患者。对细菌和人口统计学因素进行分析，以确定与治疗失败和复发的相关性。
仅根据常规方案痰涂片显微镜检查（第 2、5 和 8 个月），239 例患者中（12.6%）有 30 例根据世界卫生组织（WHO）标准出现不良结局。在 2 年随访期间，又有 39 例患者出现不良结局，2 年随访期间，239 例耐异烟肼患者中共有 69 例（28.9%）出现不良结局。在 2 年随访期间，耐异烟肼结核病病例中，北京家族是唯一与不良结局显著相关的因素（调整后的 OR=3.16[1.54-6.47]，P=0.002）。
旧的 8 个月方案下，1/3 的耐异烟肼结核病病例在 2 年内出现治疗失败/复发。超过一半的病例未通过标准的世卫组织推荐的治疗监测方法检出。需要加强对耐异烟肼结核病早期诊断和最佳方案的研究。结核分枝杆菌北京基因型的感染是导致治疗后细菌持续存在、2 年内出现治疗失败/复发的一个重要危险因素。北京基因型菌株对标准药物治疗方案的耐受性增加的潜在机制尚不清楚。
