{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:13:55Z","timestamp":1793121235170,"version":"4.5.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006191","name":"Eskisehir Osmangazi University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006191","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Antibiotic-associated diarrhea (AAD) is one of the side effects that occur during and after antibiotic use. Some probiotics have strain-specific beneficial effects on AAD development when used in combination with antibiotics. The aim of this study was to evaluate the effect of <jats:italic>Limosilactobacillus reuteri<\/jats:italic> DSM 17938 on the prevention of AAD in children. This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial in T\u00fcrkiye between 2017\u20132019, among outpatient children with acute otitis media (AOM) or acute rhinosinusitis (ARS). Group 1 (n\u2009=\u2009330) received amoxicillin-clavulanate and <jats:italic>L. reuteri<\/jats:italic> DSM 17938 (2\u2009\u00d7\u200910<jats:sup>8<\/jats:sup>\u00a0CFU) and Group 2 (n\u2009=\u2009324) received amoxicillin-clavulanate and a placebo during the antibiotic treatment or continued for 21\u00a0days after antibiotic cessation. The primary end point of this study was the percentage of children with AAD in the first 14, 21, and 56\u00a0days of follow-up. Secondary endpoints are the percentage of children with AAD regarding the AOM vs ARS, amoxicillin-clavulanate dose, age groups, and the comparison between 14- and 21-days use of <jats:italic>L. reuteri<\/jats:italic>. The percentage of children with AAD was significantly lower in the <jats:italic>L. reuteri<\/jats:italic> group compared to the placebo group at 14\u00a0days (7.9% vs. 16.7%; RR: 0.47, 95%CI 0.30\u20130.7; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001); at 21\u00a0days (8.8% vs. 17.9%; RR: 0.49, 95%CI 0.32\u20130.74;<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001); and at 56\u00a0days (9.1% vs. 19.6%; RR: 0.46, 95%CI 0.30\u20130.69;<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). The incidence of AAD was also significantly lower in the <jats:italic>L. reuteri<\/jats:italic> group at 14, 21 and 56\u00a0days among children aged between 6\u201324\u00a0months (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) or children with AOM (p\u2009=\u20090.0001,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001,<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). When AAD was observed, the mean duration of diarrhea was longer in the placebo group(<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions:<\/jats:italic> This first study with <jats:italic>L. reuteri<\/jats:italic> DSM 17938 in a large pediatric outpatient setting showed significant reduction of AAD during the first 14\u00a0days of antibiotic use and the 8-week follow-up period.<\/jats:p>\n          <jats:p>\n            <jats:italic>Trial Registration<\/jats:italic>: NCT02765217 (First Submitted 02.05.2016) (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT02765217?term=NCT02765217&amp;rank=1\" ext-link-type=\"uri\">https:\/\/clinicaltrials.gov\/study\/NCT02765217?term=NCT02765217&amp;rank=1<\/jats:ext-link>).\n<jats:table-wrap>\n              <jats:table>\n                <jats:tbody>\n                  <jats:tr>\n                    <jats:td colspan=\"2\">\n                      <jats:bold>What is known:<\/jats:bold>\u2022 <jats:italic>Antibiotic associated diarrhea (AAD) is one of the common complications of antibiotic use in children and selected probiotics may have a strain-specific effect to prevent AAD<\/jats:italic>\u2022 <jats:italic>There are limited studies about the effects of Limosilactobacillus reuteri DSM 17938 on AAD, and no study available in pediatric outpatient setting.<\/jats:italic>\n                    <\/jats:td>\n                  <\/jats:tr>\n                  <jats:tr>\n                    <jats:td colspan=\"2\">\n                      <jats:bold>What is new:<\/jats:bold>\u2022 <jats:italic>Limosilactobacillus reuteri DSM 17938 significantly reduced the incidence of AAD in children at 14-, 21-, and 56- days follow-up.<\/jats:italic>\u2022 <jats:italic>The effect is mainly observed in children aged between 6 and 24 months or children with AOM.<\/jats:italic>\n                    <\/jats:td>\n                  <\/jats:tr>\n                <\/jats:tbody>\n              <\/jats:table>\n            <\/jats:table-wrap>\n          <\/jats:p>","DOI":"10.1007\/s00431-025-06249-8","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:20:43Z","timestamp":1749450043000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effect of Limosilactobacillus reuteri DSM17938 to prevent antibiotic-associated diarrhea in children: prospective, multi-center, randomized, placebo-controlled clinical trial (PEARL Study)"],"prefix":"10.1007","volume":"184","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-0134","authenticated-orcid":false,"given":"Ener Cagri","family":"Dinleyici","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metehan","family":"Ozen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirin","family":"Guven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazan","family":"Dalgic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adem","family":"Karbuz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Sutcu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozden","family":"Turel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Nur","family":"Oz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulviye","family":"Kirli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevgi","family":"Yasar Durmus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet Sami","family":"Yazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep Ebru","family":"Cakin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvan","family":"Vandenplas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ates","family":"Kara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"issue":"3","key":"6249_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41575-024-01023-x","volume":"22","author":"H Szajewska","year":"2025","unstructured":"Szajewska H, Scott KP, de Meij T et al (2025) Antibiotic-perturbed microbiota and the role of probiotics. 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MO has acted as a consultant and keynote speaker for Sanofi Pasteur Vaccines, Pfizer Vaccines, Biogaia, HiPP, Nestl\u00e9 Nutrition, Sanofi CHC, Nobel Pharma and Abdi Ibrahim Pharma. YV participated as a clinical investigator, and\/or advisory board member, and\/or consultant, and\/or speaker for Abbott Nutrition, Alba Health, Arla, BioGaia, Danone, ELSE Nutrition, Friesland Campina, Nestle Health Science, Nestle Nutrition Institute, Nutricia, Pileje, United Pharmaceuticals (Novalac). Other authors declared no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"408"}}