英国伦敦大学圣乔治学院Mike Sharland团队研究了阿莫西林剂量和疗程对社区获得性肺炎患儿抗生素再治疗需求的影响。2021年11月2日出版的《美国医学会杂志》发表了这项成果。

社区获得性肺炎（CAP）患儿口服阿莫西林的最佳剂量和持续时间尚不清楚。

为了确定低剂量阿莫西林是否优于高剂量，以及3天治疗是否优于7天，研究组进行了一项多中心、随机、2 × 2析因非劣效性试验，2017年2月至2019年4月，共招募了824名6个月及以上儿童，临床诊断为CAP，均在英国28家医院和爱尔兰1家医院的急诊科和住院病房出院时接受阿莫西林治疗，最后一次随访时间为2019年5月21日。

将干预儿童按1：1的比例随机接受低剂量口服阿莫西林（35-50 mg/kg/d；410例）或更高剂量（70-90 mg/kg/d；404例），持续时间较短（3天；413例）或持续时间较长（7天；401例）。主要结局是随机分组后28天内，临床指示对呼吸道感染进行抗生素再治疗的需求。非劣效边缘为8%。次要结局包括9项父母报告的CAP症状的严重程度/持续时间、3项抗生素相关不良事件以及定植肺炎链球菌分离株的表型耐药性。

在824名随机分为4组中的参与者中，814名接受了至少1剂试验药物，中位年龄为2.5岁，421名（52%）为男性，393名（48%）为女性，共有789名（97%）获得了主要结局数据。低剂量组的主要结局发生率为12.6%，高剂量组为12.4%，3天治疗组为12.5%，7天治疗组为12.5%。

两组均表现出非劣效性，剂量和持续时间之间无明显交互作用。在14个预先指定的次要终点中，3天治疗组的中位咳嗽持续时间和因咳嗽干扰睡眠的时间均显著高于7天治疗组。在重度CAP儿童亚组中，低剂量组中有17.3%的参与者发生主要结局，高剂量组中有13.5%；3天治疗组中有16.0%，7天治疗组中有14.8%。

研究结果表明，在从急诊室或医院病房（48小时内）出院的CAP儿童中，在抗生素再治疗的需求方面，低剂量门诊口服阿莫西林的疗效并不比高剂量差，持续治疗3天的疗效也不比7天差。

附：英文原文

Title: Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial

Author: Julia A. Bielicki, Wolfgang Sthr, Sam Barratt, David Dunn, Nishdha Naufal, Damian Roland, Kate Sturgeon, Adam Finn, Juan Pablo Rodriguez-Ruiz, Surbhi Malhotra-Kumar, Colin Powell, Saul N. Faust, Anastasia E. Alcock, Dani Hall, Gisela Robinson, Daniel B. Hawcutt, Mark D. Lyttle, Diana M. Gibb, Mike Sharland, PERUKI, GAPRUKI, and the CAP-IT Trial Group, Elizabeth Molyneux, Chris C Butler, Alan Smyth, Catherine Prichard, Tim E.A Peto, Simon Cousens, Stuart Logan, Alasdair Bamford, Anna Turkova, Anna L Goodman, Felicity Fitzgerald, Paul S Little, Julie Robotham, Mandy Wan, Nigel Klein, Louise Rogers, Elia Vitale, Matthew Rotheram, Rachel Wright, Elizabeth Lee, Udeme Ohia, Stuart Hartshorn, Deepthi Jyothish, Juliet Hopkins, James G Ross, Poonam Patel, Hannah Fletcher, Kribashnie Nundlall, Jamie Carungcong, Rhian Bull, Nabila Burney, Patricia Correia Da Costa, Stefania Vergnano, Beth Walton, Alice Smith, Michelle Ross, Lucie Aplin, Sarah Sheedy, Gurnie Kaur, Jeff Morgan, Jennifer Muller, Gail Marshall, Godfrey Nyamugunduru, John C Furness, Dawn Eggington, Susannah J Holt, John Gibbs, Caroline Burchett, Caroline Lonsdale, Sarah De-Beger, Ronny Cheung, Alyce B Sheedy, Mohammad Ahmad

Issue&Volume: 2021/11/02

Abstract:

Importance  The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.

Objective  To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.

Design, Setting, and Participants  Multicenter, randomized, 2×2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.

Interventions  Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n=410) or higher dose (70-90 mg/kg/d; n=404), for a shorter duration (3 days; n=413) or a longer duration (7 days; n=401).

Main Outcomes and Measures  The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.

Results  Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI –∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI –∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P=.63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P=.04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P=.03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, –∞ to10%]; P value for interaction=.18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, –∞ to 7.4%]; P value for interaction=.73).

Conclusions and Relevance  Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

DOI: 10.1001/jama.2021.17843

Source: https://jamanetwork.com/journals/jama/article-abstract/2785716