Craig Jonathan C, Simpson Judy M, Williams Gabrielle J, Lowe Alison, Reynolds Graham J, McTaggart Steven J, Hodson Elisabeth M, Carapetis Jonathan R, Cranswick Noel E, Smith Grahame, Irwig Les M, Caldwell Patrina H Y, Hamilton Sana, Roy Leslie P
Screening and Test Evaluation Program and the School of Public Health, University of Sydney, Sydney, NSW, Australia.
N Engl J Med. 2009 Oct 29;361(18):1748-59. doi: 10.1056/NEJMoa0902295.
Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children.
We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data.
From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions).
Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)
抗生素被广泛用于儿童以预防尿路感染，但缺乏足够样本量且采用安慰剂对照的关于其疗效的试验。这项来自澳大利亚四个中心的研究探讨了低剂量持续口服抗生素疗法能否预防易患尿路感染的儿童发生感染。
我们将18岁以下曾有过一次或多次经微生物学证实的尿路感染的儿童随机分组，分别给予每日一次的甲氧苄啶 - 磺胺甲恶唑混悬液（剂量为每千克体重2毫克甲氧苄啶加10毫克磺胺甲恶唑）或安慰剂，为期12个月。主要结局是经微生物学证实的有症状尿路感染。采用事件发生时间数据进行意向性分析。
从1998年12月至2007年3月，共有576名儿童（计划纳入780名）接受了随机分组。入组时的中位年龄为14个月；64%的患者为女孩，42%已知有膀胱输尿管反流（其中53%为至少III级），71%在首次诊断尿路感染后入组。在研究期间，接受甲氧苄啶 - 磺胺甲恶唑治疗的288例患者中有36例（13%）发生尿路感染（抗生素组），安慰剂组288例患者中有55例（19%）发生尿路感染（抗生素组的风险比为0.61；95%置信区间为0.40至0.93；对数秩检验P = 0.02）。在抗生素组中，尿路感染绝对风险的降低（6个百分点）在所有亚组患者中似乎是一致的（所有交互作用P≥0.20）。
长期低剂量的甲氧苄啶 - 磺胺甲恶唑与易患尿路感染的儿童尿路感染次数减少有关。治疗效果在各亚组中似乎是一致的，但程度适中。（澳大利亚和新西兰临床试验注册编号，ACTRN12608000470392。）
