英国南安普顿大学Paul Little研究了英国初级保健儿童下呼吸道感染抗生素治疗的效果。该研究于2021年9月22日发表于《柳叶刀》杂志上。

抗生素耐药是一个全球性的公共健康威胁。抗生素通常用于患有无并发症下呼吸道感染（LRTIs）的儿童，但从总体或关键临床亚组的随机对照试验中几乎没有证据表明抗生素的有效性。研究组评估了阿莫西林是否能缩短初级保健、总体和关键临床亚组中出现无并发症（非肺炎）LRTI的儿童中度不良症状的持续时间。

研究组在英国的56家普通诊所进行了一项双盲、随机、安慰剂对照试验，招募6个月至12岁的儿童，他们在初级保健中出现急性无并发症LRTI，被判定为具有传染性，临床上未怀疑肺炎，症状持续时间不超过21天。将其按1：1的比例随机分组，分别接受阿莫西林或安慰剂口服治疗，持续7天。主要结局是症状评分为中度及以上严重症状的持续时间长达28天或直到症状缓解。主要结局和安全性在意向治疗人群中进行评估。

2016年11月9日至2020年3月17日，432名儿童被随机分配到抗生素组（221例）或安慰剂组（211例）。317例（73%）患者有完整的症状持续时间数据；缺失的数据用于初步分析。两组之间中度及以上严重症状的平均持续时间相似，其中抗生素组为5天，安慰剂组为6天。在五个预先指定的临床亚组（有胸部体征、发烧、医生评定的不适、痰或胸闷以及呼吸短促的患者）中，治疗组之间的主要结局没有差异。完整病例分析和按方案分析得出的估计值与估算数据分析相似。

研究结果表明，阿莫西林治疗儿童无并发症胸部感染的临床效果可能不全面，也可能对常用抗生素的主要亚组无效。除非怀疑患有肺炎，否则临床医生应提供安全建议，不应为大多数出现胸部感染的儿童开抗生素处方。

附：英文原文

Title: Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial

Author: Paul Little, Nick A Francis, Beth Stuart, Gilly OReilly, Natalie Thompson, Taeko Becque, Alastair D Hay, Kay Wang, Michael Sharland, Anthony Harnden, Guiqing Yao, James Raftery, Shihua Zhu, Joseph Little, Charlotte Hookham, Kate Rowley, Joanne Euden, Kim Harman, Samuel Coenen, Robert C Read, Catherine Woods, Christopher C Butler, Saul N Faust, Geraldine Leydon, Mandy Wan, Kerenza Hood, Jane Whitehurst, Samantha Richards-Hall, Peter Smith, Michael Thomas, Michael Moore, Theo Verheij

Issue&Volume: 2021-09-22

Abstract:

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.

DOI: 10.1016/S0140-6736(21)01431-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01431-8/fulltext