{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:24:21Z","timestamp":1793147061396,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    The formation of a biofilm on the implant surface is a major cause of intractable implant-associated infection. To investigate the antibiotic concentration needed to eradicate the bacteria inside a biofilm, the minimum biofilm eradication concentration (MBEC) has been used, mostly against\n                    <jats:italic>in vitro<\/jats:italic>\n                    biofilms on plastic surfaces. To produce a more clinically relevant environment, an MBEC assay against biofilms on stainless-steel implants formed in a rat femoral infection model was developed. The rats were implanted with stainless steel screws contaminated by two\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    strains (UAMS-1, methicillin-sensitive\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    ; USA300LAC, methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    ) and euthanized on days 3 and 14. Implants were harvested, washed, and incubated with various concentrations (64\u20134096 \u03bcg\/mL) of gentamicin (GM), vancomycin (VA), or cefazolin (CZ) with or without an accompanying systemic treatment dose of VA (20 \u03bcg\/mL) or rifampicin (RF) (1.5 \u03bcg\/mL) for 24\u00a0h. The implant was vortexed and sonicated, the biofilm was removed, and the implant was re-incubated to determine bacterial recovery. MBEC on the removed biofilm and implant was defined as\n                    <jats:italic>in vivo<\/jats:italic>\n                    MBEC and\n                    <jats:italic>in vivo<\/jats:italic>\n                    implant MBEC, respectively, and the concentrations of 100% and 60% eradication were defined as MBEC\n                    <jats:sub>100<\/jats:sub>\n                    and MBEC\n                    <jats:sub>60<\/jats:sub>\n                    , respectively. As for\n                    <jats:italic>in vivo<\/jats:italic>\n                    MBEC, MBEC\n                    <jats:sub>100<\/jats:sub>\n                    of GM was 256\u20131024 \u03bcg\/mL, but that of VA and CZ ranged from 2048\u20134096 \u03bcg\/mL. Surprisingly, the\n                    <jats:italic>in vivo<\/jats:italic>\n                    implant MBEC was much higher, ranging from 2048 \u03bcg\/mL to more than 4096 \u03bcg\/mL. The addition of RF, not VA, as a secondary antibiotic was effective, and MBEC\n                    <jats:sub>60<\/jats:sub>\n                    on day 3 USA300LAC biofilm was reduced from 1024 \u03bcg\/mL with GM alone to 128 \u03bcg\/mL in combination with RF and the MBEC\n                    <jats:sub>60<\/jats:sub>\n                    on day 14 USA300LAC biofilm was reduced from 2048 \u03bcg\/mL in GM alone to 256 \u03bcg\/mL in combination with RF. In conclusion, a novel MBEC assay for\n                    <jats:italic>in vivo<\/jats:italic>\n                    biofilms on orthopedic implants was developed. GM was the most effective against both methicillin-sensitive and methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , in\n                    <jats:italic>in vivo<\/jats:italic>\n                    biofilms, and the addition of a systemic concentration of RF reduced MBEC of GM. Early initiation of treatment is desired because the required concentration of antibiotics increases with biofilm maturation.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2022.896978","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T09:29:06Z","timestamp":1656667746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":64,"title":["Estimation of Minimum Biofilm Eradication Concentration (MBEC) on In Vivo Biofilm on Orthopedic Implants in a Rodent Femoral Infection Model"],"prefix":"10.3389","volume":"12","author":[{"given":"Yu","family":"Okae","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Nishitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Tomizawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoo","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/infdis\/jiu007","article-title":"Impact of Vancomycin on sarA-Mediated Biofilm Formation: Role in Persistent Endovascular Infections Due to Methicillin-Resistant Staphylococcus Aureus","volume":"209","author":"Abdelhady","year":"2014","journal-title":"J. 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