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Considering the increasing risk for antimicrobial resistance with longer antibiotic regimes, it is important to establish the optimal antibiotic protocol with a maximum antimicrobial benefit and minimum risk for adverse effects. The aim of the study was to evaluate the microbiological and inflammatory outcomes 12-months after a 3-\/7-day systemic antibiotic protocol [amoxicillin (AMX)\u2009+\u2009metronidazole (MET)] adjunctive to subgingival debridement in severe periodontitis compared to mechanical treatment alone. From the initially treated 102 patients, 75 subjects (Placebo group: n\u2009=\u200926; 3-day AMX\u2009+\u2009MET group: n\u2009=\u200924; 7-day AMX\u2009+\u2009MET group: n\u2009=\u200925) completed the 12-month examination. Clinical parameters, eight periodontal pathogens and inflammatory markers were determined at baseline and 3-, 6-, 12-months after therapy using real-time PCR and ELISA respectively. After 6\u00a0months, several periodontopathogens were significantly more reduced in the two antibiotic groups compared to placebo (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). After 1\u00a0year, both antibiotic protocols showed significant reductions and detection of the keystone pathogen <jats:italic>P. g<\/jats:italic>ingivalis compared to placebo. Antibiotic protocols, smoking, disease severity, baseline-BOP, -CAL and -IL-1\u03b2, as well as detection of <jats:italic>T. denticola<\/jats:italic> at 12-months significantly influenced the residual number of deep sites. The present data indicate that the systemic use of both short and longer antibiotic protocols (AMX\u2009+\u2009MET) adjunctive to nonsurgical periodontal therapy lead to higher microbiological improvements compared to subgingival debridement alone. The two investigated antibiotic protocols led to comparable microbiological and inflammatory results.<\/jats:p>","DOI":"10.1038\/s41598-020-73054-8","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T10:05:01Z","timestamp":1601546701000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Microbiological and host-derived biomarker evaluation following non-surgical periodontal therapy with short-term administration of systemic antimicrobials: secondary outcomes of an RCT"],"prefix":"10.1038","volume":"10","author":[{"given":"Raluca","family":"Cosgarea","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Eick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Jepsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. 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