Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia

作者：Julia Bielicki, Wolfgang Stöhr, Sam Barratt, David Dunn, Nishdha Naufal, Damian Roland, Kate Sturgeon, Adam Finn, Juan Pablo Rodríguez-Ruiz, Surbhi Malhotra‐Kumar, Colin Powell, Saul N. Faust, Anastasia 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, Christopher Butler, Alan R Smyth, Catherine Prichard, Tim Peto, Simon Cousens, Stuart Logan, Alasdair Bamford, Anna Turkova, Anna L. Goodman, Felicity Fitzgerald, Paul Little, Julie V. 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 Costa, Stefania Vergnano, Beth Walton, Alice C. Smith, Michelle Ross, Lucie Aplin, Sarah Sheedy, Gurnie Kaur, Jeffrey R. Morgan, Jennifer Muller, Gail Marshall, G Nyamugunduru, John Furness, Dawn Eggington, Susannah J. Holt, John Gibbs, Caroline Burchett, Caroline Lonsdale, Sarah De-Beger, Ronny Cheung, Alyce B Sheedy, Mohammad Ahmad, Zoe Stockwell, Sarah Giwa, Arshid Murad, Katherine Jerman, Joanna Green, Chris Bird, Tanya Baron, Shelley Segal, Sally Beer, María José García, Dom Georgiou, Kirsten Beadon, José Luis Martínez, Fleur Cantle, Hannah Eastman, Paul Riozzi, Hannah Cotton, Niall Mullen, Rhona McCrone, Paul Corrigan, Gemma Salt, Louise Fairlie, Andrew M. Smith, Lizzie Starkey, Melanie Hayman, Séan O’Riordan, Alice Downes, Majorie Allen, Louise A. Turner, Donna Ellis, Srini Bandi, Rekha Patel, Chris Gough, Megan K. McAulay, Louise Conner, Sharryn Gardner, Zena Haslam, Moira Morrison, Michael Barrett, Madeleine Niermeyer, Ellen M. Barry, Emily Walton, Akshat Kapur, Vivien Richmond, Steven Foster, RM Bland, Ashleigh Neil, Barry Milligan, H. M. Bannister, Ben Bloom, Ami Parikh, Imogen Skene, Helen T. Power, Olivia Boulton, Raine Astin-Chamberlain, David B. Smith, Jonathon Walters, Daniel Martín, Lyrics Noba, Katherine Potier, Fiona Borland, Jill Wilson, Zainab Suleman, Judith Gilchrist, N. West, Jayne Evans, Juliet Morecombe, Paul T. Heath, Yasser Iqbal, Malte Kohns Vasconcelos, Elena Stefanova, Claire Womack, Ian Maconochie, Suzanne Laing, Rikke Jørgensen, Maggie Nyirenda, Sophie Keers, Samia Pilgrim, Emma Gardiner, Katrina Cathie, Jane Bayreuther, Ruth Ensom, Emily K. Cornish, Elizabeth-Jayne L. Herrieven, William Townend, Leanne Sherris, Paul Williams · 发表于：JAMA · 年份：2021 · DOI：10.1001/jama.2021.17843 · 被引用次数：115 · 研究领域：Pneumonia and Respiratory Infections、Antibiotic Use and Resistance、Respiratory viral infections research

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...