Desmond Tutu Tuberculosis Centre.
Clin Infect Dis. 2013 Dec;57(12):1676-84. doi: 10.1093/cid/cit655. Epub 2013 Sep 24.
Evidence is limited to guide the management of children exposed to multidrug-resistant (MDR) tuberculosis. We aimed to study the tolerability and toxicity of a standard preventive therapy regimen given to children exposed to infectious MDR tuberculosis, and explore risk factors for poor outcome.
In this prospective cohort study in the Western Cape, South Africa, children <5 years of age, or human immunodeficiency virus (HIV)-positive children aged <15 years, were recruited from May 2010 through April 2011 if exposed to an ofloxacin-susceptible, MDR tuberculosis source case. Children were started on preventive therapy as per local guidance: ofloxacin, ethambutol, and high-dose isoniazid for 6 months. Standardized measures of adherence and adverse events were recorded; poor outcome was defined as incident tuberculosis or death from any cause.
One hundred eighty-six children were included, with a median age of 34 months (interquartile range, 14-47 months). Of 179 children tested for HIV, 9 (5.0%) were positive. Adherence was good in 141 (75.8%) children. Only 7 (3.7%) children developed grade 3 adverse events. One child (0.5%) died and 6 (3.2%) developed incident tuberculosis during 219 patient-years of observation time. Factors associated with poor outcome were age <1 year (rate ratio [RR], 10.1; 95% confidence interval [CI], 1.65-105.8; P = .009), HIV-positive status (RR, 10.6; 95% CI, 1.01-64.9; P = .049), exposure to multiple source cases (RR, 6.75; 95% CI, 1.11-70.9; P = .036) and poor adherence (RR, 7.50; 95% CI, 1.23-78.7; P = .026).
This 3-drug preventive therapy regimen was well tolerated and few children developed tuberculosis or died if adherent to therapy. The provision of preventive therapy to vulnerable children following exposure to MDR tuberculosis should be considered.
目前的证据还不足以指导儿童暴露于耐多药（MDR）结核病时的管理。本研究旨在研究标准预防治疗方案用于暴露于传染性耐多药结核病的儿童的安全性和毒性，并探讨不良结局的相关风险因素。
本研究为前瞻性队列研究，于 2010 年 5 月至 2011 年 4 月在南非西开普省开展，招募对象为接触了氟喹诺酮类药物敏感、耐多药结核分枝杆菌源病例的年龄<5 岁的儿童或人类免疫缺陷病毒（HIV）阳性且年龄<15 岁的儿童。根据当地指南，为接触源病例的儿童开始预防性治疗：左氧氟沙星、乙胺丁醇和高剂量异烟肼治疗 6 个月。记录了标准化的依从性和不良事件测量；不良结局定义为发生结核病或任何原因导致的死亡。
共纳入 186 例儿童，中位年龄为 34 个月（四分位距，14-47 个月）。179 例接受 HIV 检测的儿童中，9 例（5.0%）为阳性。141 例（75.8%）儿童的依从性良好。仅 7 例（3.7%）儿童出现 3 级不良事件。1 例（0.5%）儿童死亡，6 例（3.2%）儿童在 219 患者-年的观察时间内发生了结核病。不良结局的相关因素包括年龄<1 岁（比值比[RR]，10.1；95%置信区间[CI]，1.65-105.8；P =.009）、HIV 阳性（RR，10.6；95% CI，1.01-64.9；P =.049）、接触多个源病例（RR，6.75；95% CI，1.11-70.9；P =.036）和依从性差（RR，7.50；95% CI，1.23-78.7；P =.026）。
本研究使用的 3 种药物预防治疗方案具有良好的耐受性，如果儿童能够坚持治疗，很少会发生结核病或死亡。应考虑为接触耐多药结核病的弱势儿童提供预防治疗。
