{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:31:47Z","timestamp":1777987907665,"version":"3.51.4"},"update-to":[{"DOI":"10.3310\/nihropenres.14103.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000}}],"reference-count":26,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/open-government-licence\/version\/3\/"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment Programme","doi-asserted-by":"publisher","award":["NIHR152733"],"award-info":[{"award-number":["NIHR152733"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns3:p>Background Urinary tract infections (UTIs) are the most common serious bacterial infections in febrile infants. Current UK guidelines recommend parenteral antibiotics for infants under three months with suspected UTI, despite evidence supporting oral therapy in low-risk infants. Objectives To assess whether oral antibiotics are non-inferior to parenteral antibiotics for treating suspected UTIs based on treatment failure, need for additional therapy, and secondary outcomes. Design Multicentre, randomised controlled, open-label, non-inferiority trial with embedded internal pilot. Setting Twenty one paediatric emergency departments and assessment units across the UK. Participants Infants aged 29\u201390 days with suspected UTI, abnormal urinalysis, and low risk of invasive bacterial infection. Exclusion criteria included prematurity, prior hospitalisation, structural renal abnormalities, and clinical signs of sepsis or meningitis. Interventions Participants were randomised 1:1 to receive either oral antibiotics or standard care with intravenous (IV) antibiotics for 36\u201348 hours pending urine culture results. Main outcome measures The primary outcome was the requirement for additional parenteral antibiotics within seven days of randomisation. A range of secondary outcomes were also planned, including treatment failure, time to recovery, adverse events, antibiotic adherence, quality of life, family impact, and healthcare resource use. Feasibility outcomes collected during the internal pilot included recruitment rate, site activation, protocol adherence, and retention. Clinical outcomes were collected but not powered for formal comparison. Results 27 participants were recruited between 20 May 2024 and 13 March 2025 (which included the 6 month internal pilot), representing 27% of the pilot target. Protocol adherence was high, and no cases of meningitis occurred. Two cases of bacteraemia (one per randomised group) had uncomplicated clinical courses. Oral therapy was associated with shorter hospital stays and reduced parental time off work. Conclusions While trial procedures were successfully implemented, recruitment challenges suggest that a larger randomised trial of this treatment comparison is not feasible in this setting. Trial management Northern Ireland Clinical Trials Unit (NICTU) Trial registration ISRCTN Clinical Trials Registry, ISRCTN10907780, Trial Dates 20 May 2024 to 13 March 2025<\/ns3:p>","DOI":"10.3310\/nihropenres.14103.2","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T04:29:09Z","timestamp":1771561749000},"page":"104","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Empirical oral AntibioticS for possible UTI in well appearing Young febrile infants (EASY)"],"prefix":"10.3310","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-7716","authenticated-orcid":false,"given":"Thomas","family":"Waterfield","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronan","family":"McMullan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8634-7210","authenticated-orcid":false,"given":"Mark 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.15492.r39506, Ghassan Ghssein, Lebanese University, Beirut, 20 Feb 2026, version 2, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-104\/v2#referee-response-39506","order":0,"name":"referee-response-39506","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15336.r38903, Kazuki Iio, Tokyo Metropolitan Children\u2019s Medical Center, Fuchu, Tokyo, 20 Jan 2026, version 1, 1 approved, 1 not approved","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-104\/v1#referee-response-38903","order":1,"name":"referee-response-38903","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Thomas Waterfield<\/b>; \n<i>Posted: 20 Jan 2026<\/i>; Response to Reviewer  We thank the reviewer for their thoughtful and constructive comments, which have helped improve the clarity and interpretation of the manuscript. We have addressed each point below.  \n<b>Comment 1: Discrepancies in guideline recommendations for oral antibiotics<\/b> \n<i>Reviewer comment:<\/i> I recommend revising the final paragraph of this section, as there are discrepancies among existing recommendations regarding the use of oral antibiotics in the population studied in this trial\u2026 \n<i>Response:<\/i> We thank the reviewer for highlighting this important point. We have revised the final paragraph to explicitly acknowledge ongoing international variation in recommendations regarding the route of antibiotic administration in young infants with suspected UTI. The amended text now contrasts American Academy of Pediatrics guidance, which supports oral antibiotic treatment in infants older than 28 days, with Swiss consensus recommendations, which advise oral therapy only in infants over 60 days of age. We now explicitly state that this lack of consensus represents a key motivation for conducting this randomised controlled trial (references 2, 23, 24).  \n<b>Comment 2: Inclusion of infants with parent-reported (subjective) fever<\/b> \n<i>Reviewer comment:<\/i> Among the inclusion criteria, I am slightly concerned about the inclusion of patients with \u201csubjective\u201d fever\u2026 \n<i>Response:<\/i> We agree that this is a reasonable concern. While parent-reported fever has lower specificity for measured fever, existing literature in febrile infants suggests that caregiver-reported fever is nevertheless associated with both documented fever and invasive bacterial infection, particularly in younger infants. Inclusion of infants with a history of fever therefore reflects real-world clinical decision-making at the point of presentation. Furthermore NICE in the UK advises that caregiver reports of subjective fever are taken seriously.&nbsp;  Reporting the proportion of participants included solely on the basis of subjective fever would indeed have been informative, and a sensitivity analysis excluding these infants was planned for the definitive trial. However, following early termination of the study after the pilot phase, the sample size was insufficient to support a meaningful sensitivity analysis.&nbsp;  \n<b>Comment 3: Method of urine collection<\/b> \n<i>Reviewer comment:<\/i> In addition, the method of urine collection should be clearly described; I assume urethral catheterization was used in this age group.  \n<i>Response:<\/i> Thank you for this comment. In contrast to some international guidance, UK NICE recommendations advise against routine invasive urine sampling in young children, and in UK practice the majority of urine samples are obtained using non-invasive clean-catch methods where feasible. Given the pragmatic, multicentre design of this trial, sites were permitted to collect urine according to local clinical policy and the treating clinician\u2019s judgement. Mandating a single method of urine collection was not considered pragmatic or reflective of real-world UK practice. The method of urine collection was recorded on the case report form, and this has now been clarified in the Trial Interventions section.  \n<b>Comment 4: Definition of treatment failure at day 28<\/b> \n<i>Reviewer comment:<\/i> Finally, treatment failure at day 28 is listed as a secondary outcome. Could the authors clarify how this outcome was defined? \n<i>Response:<\/i> Thank you for highlighting this potential ambiguity. Treatment failure at day 28 was defined using the same criteria as the primary outcome at day 7, namely the requirement for additional parenteral antibiotic therapy, but assessed at a later time point. To avoid ambiguity, we have revised the manuscript to explicitly define the day-28 secondary outcome as \u201crequirement for additional parenteral antibiotics\u201d rather than using the term treatment failure.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-104\/v2#referee-comment-3530","order":2,"name":"referee-comment-3530","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is funded by the National Institute for Health Research (NIHR) under its Health Technology Assessment Programme (Grant Reference Number NIHR152733)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":3,"name":"grant-information","label":"Grant Information"},{"value":"This open access work is licensed under the Open Government Licence v3.0.","order":0,"name":"copyright-info","label":"Copyright"}]}}