{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:48:01Z","timestamp":1784612881477,"version":"3.55.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009776","name":"McMaster University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009776","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008360","name":"Hamilton Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008360","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute appendicitis is the most common indication for emergency surgery in children. In cases of perforation, patients require post-operative intravenous antibiotics in hospital. However, some children fail to respond adequately, resulting in prolonged hospitalization. The optimal antibiotic regimen for perforated appendicitis remains uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We propose a double-blind, randomized controlled pilot trial comparing two commonly used antibiotic strategies. Eligible participants include children &lt;18 years undergoing laparoscopic appendectomy for perforated appendicitis. Following surgery, participants will be randomized to receive either: (1) piperacillin\/tazobactam; or (2) ceftriaxone and metronidazole. The sample size for the pilot study is 16 participants (i.e., 8 per group). Feasibility outcomes include recruitment rate, protocol adherence, loss to follow-up, and cost per participant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This pilot study will assess the feasibility of conducting a blinded randomized controlled trial of postoperative antibiotic therapy in children with perforated appendicitis. To date, only one randomized trial has addressed this question, but it was limited by its single-center design, lack of blinding, and susceptibility to ascertainment bias and other methodological concerns. Findings from this pilot will inform the design of a larger, multicenter study with rigorous blinding and standardized outcome assessment to determine whether piperacillin-tazobactam or ceftriaxone and metronidazole provides superior outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov: NCT05943223<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0335991","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:37:39Z","timestamp":1762540659000},"page":"e0335991","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessing the Longitudinal outcomes of Piperacillin\/tazobactam versus ceftriAxone and metronidazole for Children with perforated Appendicitis (ALPACA): A protocol for a pilot randomized controlled trial"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8665-9492","authenticated-orcid":true,"given":"Daniel","family":"Briatico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5605-8619","authenticated-orcid":true,"given":"Nadia","family":"Safa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Flageole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-2643","authenticated-orcid":true,"given":"Sarah","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4380-5402","authenticated-orcid":true,"given":"Jeffrey","family":"Pernica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Eltorki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Livingston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"issue":"4","key":"pone.0335991.ref001","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1053\/j.sempedsurg.2016.05.003","article-title":"Operative management of appendicitis","volume":"25","author":"SD St Peter","year":"2016","journal-title":"Semin Pediatr Surg"},{"issue":"47","key":"pone.0335991.ref002","doi-asserted-by":"crossref","first-page":"8799","DOI":"10.3748\/wjg.v19.i47.8799","article-title":"Acute appendicitis: what is the gold standard of treatment?","volume":"19","author":"C Ruffolo","year":"2013","journal-title":"World J Gastroenterol"},{"issue":"6","key":"pone.0335991.ref003","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1053\/j.sempedsurg.2016.10.002","article-title":"Complications in common general pediatric surgery procedures","volume":"25","author":"ME Linnaus","year":"2016","journal-title":"Semin Pediatr Surg"},{"issue":"6","key":"pone.0335991.ref004","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.jpedsurg.2008.02.018","article-title":"Single daily dosing ceftriaxone and metronidazole vs standard triple antibiotic regimen for perforated appendicitis in children: a prospective randomized trial","volume":"43","author":"SD St Peter","year":"2008","journal-title":"J Pediatr Surg"},{"issue":"3","key":"pone.0335991.ref005","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s40272-024-00630-0","article-title":"Perforated Appendicitis in Children: Management, Microbiology, and Antibiotic Stewardship","volume":"26","author":"KB Snyder","year":"2024","journal-title":"Paediatr Drugs"},{"issue":"3","key":"pone.0335991.ref006","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/SLA.0000000000005006","article-title":"IMPPACT (Intravenous Monotherapy for Postoperative Perforated Appendicitis in Children Trial): Randomized Clinical Trial of Monotherapy Versus Multi-drug Antibiotic Therapy","volume":"274","author":"J Lee","year":"2021","journal-title":"Ann Surg"},{"issue":"10","key":"pone.0335991.ref007","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jpedsurg.2021.11.009","article-title":"Ceftriaxone with Metronidazole versus Piperacillin\/Tazobactam in the management of complicated appendicitis in children: Results from a multicenter pediatric NSQIP analysis","volume":"57","author":"MA Kashtan","year":"2022","journal-title":"J Pediatr Surg"},{"issue":"6","key":"pone.0335991.ref008","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1097\/SLA.0000000000006152","article-title":"Use of Antipseudomonal Antibiotics is Not Associated With Lower Rates of Postoperative Drainage Procedures or More Favorable Culture Profiles in Children With Complicated Appendicitis: Results From a Multicenter Regional Research Consortium","volume":"279","author":"SL Cramm","year":"2024","journal-title":"Ann Surg"},{"issue":"6","key":"pone.0335991.ref009","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.jpedsurg.2023.02.027","article-title":"Postoperative Antibiotics for Complicated Appendicitis in Children: Piperacillin\/Tazobactam Versus Ceftriaxone with Metronidazole","volume":"58","author":"S Zeineddin","year":"2023","journal-title":"J Pediatr Surg"},{"issue":"14","key":"pone.0335991.ref010","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa1914433","article-title":"Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017","volume":"382","author":"JA Jernigan","year":"2020","journal-title":"N Engl J Med"},{"key":"pone.0335991.ref011","author":"Canadian Antimicrobial Resistance Alliance"},{"key":"pone.0335991.ref012","doi-asserted-by":"crossref","first-page":"572912","DOI":"10.3389\/fcimb.2020.572912","article-title":"Antibiotics as Major Disruptors of Gut 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