{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:16:41Z","timestamp":1759191401903,"version":"3.44.0"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004564","name":"Ministarstvo Prosvete, Nauke i Tehnolo\u00c5\u00a1kog Razvoja","doi-asserted-by":"publisher","award":["Grant No. 451-03-66\/2024-03\/ 200129"],"award-info":[{"award-number":["Grant No. 451-03-66\/2024-03\/ 200129"]}],"id":[{"id":"10.13039\/501100004564","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italmed","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>The primary aim of the present study was to compare the reduction in periodontal probing depth after the use of either local or systemic adjuvant antibiotics during non-surgical periodontal therapy at baseline and the six-month follow-up. Secondary aims were to compare other clinical outcomes, total bacterial count, and relative expression levels of certain pro-inflammatory mediators following the use of locally and systemically delivered adjuvant antibiotics during the initial non-surgical periodontal therapy (NSPT).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Material and methods<\/jats:title>\n<jats:p>A total of 38 periodontitis stage III grade B or C patients were randomly and equally assigned to receive either local (LA) (tazobactam + piperacillin preparation) or systemic antibiotics (SA) (amoxicillin and metronidazole combination) during NSPT. Clinical periodontal parameters (periodontal probing depth, clinical attachment level, bleeding on probing, and plaque index), and microbiological and immunological parameters: total bacterial count, and relative expression levels of IL-17 and TNF-\u03b1 were evaluated at baseline and six months after NSPT.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Both LA and SA significantly improved all clinical parameters after six months (<jats:italic>p<\/jats:italic>&lt;0.001 for all comparisons). While a significant decrease of total bacterial count was observed after LA (<jats:italic>p<\/jats:italic>=0.001) and SA treatment (<jats:italic>p<\/jats:italic>=0.013), the insignificant differences between the two groups were observed after the sixth-month follow-up (<jats:italic>p<\/jats:italic>&gt;0.05). Conversely, relative gene expression levels of IL-17 and TNF-\u03b1 did not differ significantly between LA and SA six months after the NSPT. The insignificant differences between these cytokines\u2019 relative levels were observed in both SA and LA between baseline and follow-up measurements.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The adjuvant use of piperacillin + tazobactam led to the comparable improvement of clinical, microbiological and immunological parameters to the conventional use of amoxicillin and metronidazol combination six months following the initial therapy of periodontitis. Therefore, these locally delivered antibiotics might be a promising alternative to the standard use of systemic amoxicillin and metronidazol combination during initial therapy of stage III periodontitis.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0333342","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T17:29:32Z","timestamp":1759166972000},"page":"e0333342","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring local adjuvant antibiotics as viable alternative to systemic antibiotics in non-surgical periodontal therapy: Clinical, immunological and microbiological insights"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-7848","authenticated-orcid":true,"given":"Iva","family":"Milinkovic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1379-6717","authenticated-orcid":true,"given":"Marija","family":"Vuckovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8513-9313","authenticated-orcid":true,"given":"Nadja","family":"Nikolic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Carkic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoran","family":"Aleksic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sasha","family":"Jankovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6225-7210","authenticated-orcid":true,"given":"Jelena","family":"Milasin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9439-0529","authenticated-orcid":true,"given":"Ana","family":"Djinic Krasavcevic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"pone.0333342.ref001","doi-asserted-by":"crossref","DOI":"10.1002\/JPER.17-0721","article-title":"Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the classification of periodontal and peri-implant diseases and conditions","volume":"89","author":"PN Papapanou","year":"2018","journal-title":"J Periodontol"},{"key":"pone.0333342.ref002","doi-asserted-by":"crossref","DOI":"10.1111\/jcpe.12945","article-title":"Staging and grading of periodontitis: framework and proposal of a new classification and case definition","volume":"45","author":"MS Tonetti","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"2","key":"pone.0333342.ref003","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3109\/03008207.2016.1140152","article-title":"The osteoimmunology of alveolar bone loss","volume":"57","author":"KA Tompkins","year":"2016","journal-title":"Connect Tissue Res"},{"issue":"1","key":"pone.0333342.ref004","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1902\/jop.2009.070465","article-title":"Antimicrobial photodynamic therapy in the non\u2010surgical treatment of aggressive periodontitis: cytokine profile in gingival crevicular fluid, preliminary results","volume":"80","author":"RR de Oliveira","year":"2009","journal-title":"J Periodontol"},{"issue":"2","key":"pone.0333342.ref005","article-title":"Inflammatory cytokines interleukin-1\u03b2 and tumour necrosis factor-\u03b1 - Novel biomarkers for the detection of periodontal diseases: a literature review","volume":"7","author":"FIF Gomes","year":"2016","journal-title":"J Oral Maxillofac Res"},{"issue":"3","key":"pone.0333342.ref006","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s11914-017-0358-z","article-title":"TNF and bone remodeling","volume":"15","author":"B Zhao","year":"2017","journal-title":"Curr Osteoporos Rep"},{"issue":"7","key":"pone.0333342.ref007","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/odi.12598","article-title":"IL\u201017: overview and role in oral immunity and microbiome","volume":"23","author":"L Abusleme","year":"2016","journal-title":"Oral Diseases"},{"issue":"6","key":"pone.0333342.ref008","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1177\/0022034515583533","article-title":"Inborn errors in immunity: unique natural models to dissect oral immunity","volume":"94","author":"NM Moutsopoulos","year":"2015","journal-title":"J Dent Res"},{"key":"pone.0333342.ref009","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/jcpe.13245","article-title":"Subgingival instrumentation for treatment of periodontitis. 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