{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T07:13:58Z","timestamp":1771485238975,"version":"3.50.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Graduate School of Health, Aarhus University"},{"DOI":"10.13039\/501100002739","name":"Aarhus Universitets Forskningsfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021817","name":"Knud og Edith Eriksens Mindefond","doi-asserted-by":"publisher","award":["62786"],"award-info":[{"award-number":["62786"]}],"id":[{"id":"10.13039\/501100021817","id-type":"DOI","asserted-by":"publisher"}]}],"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>We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log<jats:sup>10<\/jats:sup> colony forming units (CFU) of methicillin resistant <jats:italic>Staphylococcus aureus<\/jats:italic>. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log<jats:sup>10<\/jats:sup> CFU\/mL, p = 0.0011), and both the procedure and infection were well tolerated.<\/jats:p>\n<jats:p>Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log<jats:sup>10<\/jats:sup> CFU\/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log<jats:sup>10<\/jats:sup> CFU\/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0287671","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T17:27:08Z","timestamp":1689701228000},"page":"e0287671","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fibrinolytic and antibiotic treatment of prosthetic vascular graft infections in a novel rat model"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-1621","authenticated-orcid":true,"given":"Mikkel Illemann","family":"Johansen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2791-0122","authenticated-orcid":true,"given":"S\u00f8ren Jensen","family":"Rahbek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00f8ren","family":"Jensen-Fangel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel Antonio S.","family":"Minero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise Kruse","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ole Halfdan","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lise Tornvig","family":"Erikstrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders Marthinsen","family":"Seefeldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"\u00d8stergaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rikke Louise","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nis Pedersen","family":"J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"issue":"9","key":"pone.0287671.ref001","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1086\/323130","article-title":"Device-associated infections: a macroproblem that starts with microadherence","volume":"33","author":"RO Darouiche","year":"2001","journal-title":"Clin Infect Dis"},{"issue":"Suppl 1","key":"pone.0287671.ref002","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.cmi.2014.10.024","article-title":"ESCMID guideline for the diagnosis and treatment of biofilm infections 2014","volume":"21","author":"N H\u00f8iby","year":"2015","journal-title":"Clin Microbiol Infect"},{"issue":"5","key":"pone.0287671.ref003","doi-asserted-by":"crossref","first-page":"445","DOI":"10.4161\/viru.2.5.17724","article-title":"Staphylococcus aureus biofilms: properties, regulation, and roles in human disease.","volume":"2","author":"NK Archer","year":"2011","journal-title":"Virulence"},{"issue":"9276","key":"pone.0287671.ref004","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0140-6736(01)05321-1","article-title":"Antibiotic resistance of bacteria in biofilms","volume":"358","author":"PS Stewart","year":"2001","journal-title":"Lancet"},{"issue":"4","key":"pone.0287671.ref005","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.GPP3-0023-2018","article-title":"Staphylococcal Biofilms.","volume":"6","author":"M. 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