Background

Antibiotic resistance is a global public health threat. Antibiotics are very commonly prescribed for children presenting with uncomplicated lower respiratory tract infections (LRTIs), but there is little evidence from randomised controlled trials of the effectiveness of antibiotics, both overall or among key clinical subgroups. In ARTIC PC, we assessed whether amoxicillin reduces the duration of moderately bad symptoms in children presenting with uncomplicated (non-pneumonic) LRTI in primary care, overall and in key clinical subgroups.

Methods

ARTIC PC was a double-blind, randomised, placebo-controlled trial done at 56 general practices in England. Eligible children were those aged 6 months to 12 years presenting in primary care with acute uncomplicated LRTI judged to be infective in origin, where pneumonia was not suspected clinically, with symptoms for less than 21 days. Patients were randomly assigned in a 1:1 ratio to receive amoxicillin 50 mg/kg per day or placebo oral suspension, in three divided doses orally for 7 days. Patients and investigators were masked to treatment assignment. The primary outcome was the duration of symptoms rated moderately bad or worse (measured using a validated diary) for up to 28 days or until symptoms resolved. The primary outcome and safety were assessed in the intention-to-treat population. The trial is registered with the ISRCTN Registry (ISRCTN79914298).

Findings

Between Nov 9, 2016, and March 17, 2020, 432 children (not including six who withdrew permission for use of their data after randomisation) were randomly assigned to the antibiotics group (n=221) or the placebo group (n=211). Complete data for symptom duration were available for 317 (73%) patients; missing data were imputed for the primary analysis. Median durations of moderately bad or worse symptoms were similar between the groups (5 days [IQR 4–11] in the antibiotics group vs 6 days [4–15] in the placebo group; hazard ratio [HR] 1·13 [95% CI 0·90–1·42]). No differences were seen for the primary outcome between the treatment groups in the five prespecified clinical subgroups (patients with chest signs, fever, physician rating of unwell, sputum or chest rattle, and short of breath). Estimates from complete-case analysis and a per-protocol analysis were similar to the imputed data analysis.

Interpretation

Amoxicillin for uncomplicated chest infections in children is unlikely to be clinically effective either overall or for key subgroups in whom antibiotics are commonly prescribed. Unless pneumonia is suspected, clinicians should provide safety-netting advice but not prescribe antibiotics for most children presenting with chest infections.

Funding

National Institute for Health Research.

中文翻译：

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英格兰初级保健机构儿童下呼吸道感染抗生素治疗 (ARTIC PC)：一项双盲、随机、安慰剂对照试验

背景

抗生素耐药性是全球公共卫生威胁。抗生素通常用于患有无并发症的下呼吸道感染 (LRTI) 的儿童，但几乎没有来自随机对照试验的证据表明抗生素的有效性，无论是在总体上还是在关键的临床亚组中。在 ARTIC PC 中，我们评估了阿莫西林是否能缩短在初级保健、整体和关键临床亚组中出现无并发症（非肺炎）LRTI 儿童中度不良症状的持续时间。

方法

ARTIC PC 是一项双盲、随机、安慰剂对照试验，在英格兰的 56 家全科诊所进行。符合条件的儿童年龄在 6 个月至 12 岁之间，因急性无并发症的 LRTI 在初级保健中就诊，被判断为感染源，临床上未怀疑肺炎，症状少于 21 天。患者以 1:1 的比例被随机分配接受每天 50 mg/kg 的阿莫西林或安慰剂口服混悬液，分三次口服，持续 7 天。患者和研究者对治疗分配设盲。主要结果是症状被评定为中等或更差（使用经过验证的日记测量）的持续时间长达 28 天或直到症状消失。在意向治疗人群中评估了主要结局和安全性。

发现

2016 年 11 月 9 日至 2020 年 3 月 17 日期间，432 名儿童（不包括 6 名在随机分组后撤回使用其数据的许可）被随机分配到抗生素组 (n=221) 或安慰剂组 (n=211) . 317 名 (73%) 患者的症状持续时间的完整数据可用；缺失的数据被估算用于主要分析。组间中度不良或更严重症状的中位持续时间相似（抗生素组 5 天 [IQR 4-11] vs安慰剂组 6 天 [4–15]；风险比 [HR] 1·13 [95% CI 0·90–1·42]）。在五个预先指定的临床亚组（有胸部体征、发烧、医生评价为不适、咳痰或胸部咯咯声以及呼吸急促的患者）中，治疗组之间的主要结果没有差异。来自完整病例分析和符合方案分析的估计与推算数据分析相似。

解释

阿莫西林治疗儿童无并发症的胸部感染不太可能对整体或对通常使用抗生素的关键亚组产生临床效果。除非怀疑是肺炎，否则临床医生应提供安全网建议，但不要为大多数出现胸部感染的儿童开抗生素。

资金

国家健康研究所。