{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T08:11:57Z","timestamp":1760602317983,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Internal Wroclaw Medical University","award":["SUBZ.D230.25.047"],"award-info":[{"award-number":["SUBZ.D230.25.047"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pharyngitis is a leading cause of outpatient antibiotic use, despite its typically viral or self-limiting nature. Such unnecessary antibiotic therapies are not only the cause of increasing antibiotic resistance, but also significant changes in the human microbiota in the intestines and other locations, which translate into immune disorders and an increased risk of developing several chronic diseases. Orally administered octenidine-containing lozenges provide a topical alternative; however, their effects on the host microbiota of the oral cavity, throat, and intestine remain unclear. In this study, we evaluated the antimicrobial and antibiofilm in vitro activity of octenidine lozenges against 106 microbial strains, including pathogens and commensals from the oral cavity, pharynx, and large intestine. Minimal biocidal concentrations (MBCs) and minimal biofilm eradication concentrations (MBECs) were determined under physiologically relevant exposure times: 23 min for oral contact and 24 h for intestinal transit. ADME in silico analysis confirmed the lack of absorption of octenidine through the blood\u2013brain barrier and the gastric intestinal mucosa. At concentrations achievable in saliva and the intestinal lumen, octenidine effectively eradicated in vitro all oropharyngeal pathogens while leaving intestinal commensals unaffected. Its impact on oral commensals resembled that of routine mechanical cleaning. These in vitro findings are of high translative value because they support the use of octenidine lozenges as a safe topical treatment for pharyngeal infections, \u201csore throat\u201d, without adverse effects on the gut microbiota.<\/jats:p>","DOI":"10.3390\/ijms262010045","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:04:02Z","timestamp":1760537042000},"page":"10045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Octenidine Lozenges Intended for Oral Administration Display In Vitro Activity Against Oropharyngeal Pathogens and Safety Toward Intestinal Microbiota"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7559-8903","authenticated-orcid":false,"given":"Adam","family":"Junka","sequence":"first","affiliation":[{"name":"\u201cP.U.M.A.\u201d Platform for Unique Model Application, Department of Translative Technologies, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-534 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9520-3377","authenticated-orcid":false,"given":"Malwina","family":"Bro\u017cyna","sequence":"additional","affiliation":[{"name":"\u201cP.U.M.A.\u201d Platform for Unique Model Application, Department of Translative Technologies, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-534 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-8894","authenticated-orcid":false,"given":"Pawe\u0142","family":"Krzy\u017cek","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-1048","authenticated-orcid":false,"given":"Micha\u0142","family":"Tomczyk","sequence":"additional","affiliation":[{"name":"Division of Laboratory Medicine, Department of Biology and Pharmacognosy, Faculty of Pharmacy, Medical University of Bia\u0142ystok, ul. Mickiewicza 2A, 15-222 Bia\u0142ystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6555-822X","authenticated-orcid":false,"given":"Krzysztof","family":"Krasucki","sequence":"additional","affiliation":[{"name":"Department of Morphology, Universidad de Las Palmas de Gran Canaria, 35016 Las Palmas de Gran Canaria, Spain"},{"name":"Faculty of Medical and Health Sciences, Vizja University, 1-go Sierpnia 8A, 02-134 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3206-811X","authenticated-orcid":false,"given":"Tomasz","family":"Matys","sequence":"additional","affiliation":[{"name":"Clinical Department of Angiology and Internal Disease, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Musia\u0142a","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University Hospital in Wroc\u0142aw, Borowska 213, 50-536 Wroc\u0142aw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8315-7569","authenticated-orcid":false,"given":"Marta","family":"Stafiniak","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology and Biotechnology, Division of Pharmaceutical Biology and Botany, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9675-7942","authenticated-orcid":false,"given":"Andrzej","family":"Fal","sequence":"additional","affiliation":[{"name":"Collegium Medicum, Cardinal Stefan Wyszynski University, 01-938 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global burden of bacterial antimicrobial resistance 1990\u20132021: A systematic analysis with forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"162","DOI":"10.3109\/03009734.2014.896437","article-title":"Discovery and preclinical development of new antibiotics","volume":"119","author":"Hughes","year":"2014","journal-title":"Upsala J. Med. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1001\/jamapediatrics.2014.1582","article-title":"Overprescribing and inappropriate antibiotic selection for children with pharyngitis in the United States, 1997\u20132010","volume":"168","author":"Dooling","year":"2014","journal-title":"JAMA Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/jgs.16256","article-title":"Antibiotic Stewardship for Older Adults in Ambulatory Care Settings: Addressing an Unmet Challenge","volume":"68","author":"Pulia","year":"2020","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e02192","DOI":"10.1016\/j.heliyon.2019.e02192","article-title":"Challenges of intervention, treatment, and antibiotic resistance of biofilm-forming microorganisms","volume":"5","author":"Gebreyohannes","year":"2019","journal-title":"Heliyon"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3934\/microbiol.2018.1.42","article-title":"Oral microbiome and health","volume":"4","author":"Sharma","year":"2018","journal-title":"AIMS Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.4103\/jomfp.JOMFP_304_18","article-title":"Oral microbiome: Unveiling the fundamentals","volume":"23","author":"Deo","year":"2019","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_8","unstructured":"Short, S., Bashir, H., Marshall, P., Miller, N., Olmschenk, D., Prigge, K., and Solyntjes, L. (2025, August 25). Diagnosis and Treatment of Respiratory Illness in Children and Adults. Available online: https:\/\/opis-cdn.tinkoffjournal.ru\/mercury\/ice-cream-healing-1.baqoaamqo0wb..pdf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"355","DOI":"10.12968\/jowc.2018.27.6.355","article-title":"Non-antibiotic antimicrobial interventions and antimicrobial stewardship in wound care","volume":"27","author":"Cooper","year":"2018","journal-title":"J. Wound Care"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kampf, G. (2024). Antiseptic Stewardship: Biocide Resistance and Clinical Implications, Springer. [2nd ed.].","DOI":"10.1007\/978-3-031-66074-0"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1128\/CMR.00112-16","article-title":"Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns","volume":"30","author":"Williamson","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"106146","DOI":"10.1016\/j.ijantimicag.2020.106146","article-title":"Octenidine: Novel insights into the detailed killing mechanism of Gram-negative bacteria at a cellular and molecular level","volume":"56","author":"Malanovic","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1016\/j.bpj.2021.06.027","article-title":"Unraveling the mechanism of octenidine and chlorhexidine on membranes: Does electrostatics matter?","volume":"120","author":"Rzycki","year":"2021","journal-title":"Biophys. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000314699","article-title":"Octenidine dihydrochloride, a modern antiseptic for skin, mucous membranes and wounds","volume":"23","author":"Siebert","year":"2010","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dudek, B., Bro\u017cyna, M., Karoluk, M., Frankiewicz, M., Migda\u0142, P., Szustakiewicz, K., Matys, T., Wiater, A., and Junka, A. (2024). In Vitro and In Vivo Translational Insights into the Intraoperative Use of Antiseptics and Lavage Solutions Against Microorganisms Causing Orthopedic Infections. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202411.0308.v1"},{"key":"ref_16","unstructured":"European public MRL assessment report (EPMAR) (2025, July 02). Octenidine dihydrochloride (All Mammalian Food Producing Species). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/mrl-report\/octenidine-dihydrochloride-european-public-mrl-assessment-report-epmar-committee-medicinal-products-veterinary-use_en.pdf."},{"key":"ref_17","unstructured":"(2025, July 03). Octenidine. Available online: https:\/\/go.drugbank.com\/drugs\/DB12624."},{"key":"ref_18","first-page":"1","article-title":"Review on Lozenges","volume":"2","author":"Pundir","year":"2014","journal-title":"J. Pharm. Forsch."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00611-24","DOI":"10.1128\/spectrum.00611-24","article-title":"Effects of antibiotic and disinfectant exposure on the mouse gut microbiome and immune function","volume":"12","author":"Xu","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.mib.2018.07.003","article-title":"Low diversity gut microbiota dysbiosis: Drivers, functional implications and recovery","volume":"44","author":"Kriss","year":"2018","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Long, H., Yan, L., Pu, J., Liu, Y., Zhong, X., Wang, H., Yang, L., Lou, F., Luo, S., and Zhang, Y. (2022). Multi-omics analysis reveals the effects of microbiota on oral homeostasis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1005992"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cinquini, C., Izzetti, R., Nisi, M., Gulia, F., Garcia Mira, B., and Barone, A. (2025). Limosilactobacillus reuteri Improves Healing Following Fully Impacted Tooth Extractions: Randomized Clinical Trial. Oral Dis., 1\u201313.","DOI":"10.1111\/odi.70026"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Goh, C.E., Williams, R., Gupta, N., Ho, F., Islam, I., Lai, C.W.M., Tan, K.S., and Hong, C.H.L. (2025). Effect of Limosilactobacillus reuteri Probiotic on Oral Mucositis in Patients Undergoing Head and Neck Radiation: A Randomised Trial. Oral Dis., 1\u201312.","DOI":"10.1111\/odi.70083"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/cre2.386","article-title":"Effect of octenidine mouthwash on plaque, gingivitis, and oral microbial growth: A systematic review","volume":"7","author":"Grover","year":"2021","journal-title":"Clin. Exp. Dent. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8292","DOI":"10.1038\/ncomms9292","article-title":"The outer mucus layer hosts a distinct intestinal microbial niche","volume":"6","author":"Li","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1016\/j.identj.2023.08.010","article-title":"Mouthwash Effects on the Oral Microbiome: Are They Good, Bad, or Balanced?","volume":"73","author":"Brookes","year":"2023","journal-title":"Int. Dent. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/prd.12365","article-title":"Resilience of the oral microbiome","volume":"86","author":"Wade","year":"2021","journal-title":"Periodontol. 2000"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1186\/1472-6831-6-S1-S14","article-title":"Dental plaque as a biofilm and a microbial community\u2013implications for health and disease","volume":"6","author":"Marsh","year":"2006","journal-title":"BMC Oral Health"},{"key":"ref_29","first-page":"10","article-title":"Antiseptic mouth rinses: An update on comparative effectiveness, risks and recommendations","volume":"87","author":"Osso","year":"2013","journal-title":"J. Dent. Hyg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1099\/00222615-13-1-45","article-title":"The microbial contribution to human faecal mass","volume":"13","author":"Stephen","year":"1980","journal-title":"J. Med. Microbiol."},{"key":"ref_31","first-page":"22","article-title":"Reinfusion of Gastrointestinal Secretions: The Bedside Experience","volume":"41","author":"Parrish","year":"2017","journal-title":"Pract. Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10045\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:30:14Z","timestamp":1760599814000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":31,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010045"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010045","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,10,15]]}}}