{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:21:45Z","timestamp":1790727705810,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss National Foundation","award":["#320030_176216"],"award-info":[{"award-number":["#320030_176216"]}]},{"name":"Swiss National Foundation","award":["#CR31I3_166124"],"award-info":[{"award-number":["#CR31I3_166124"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background. Recurrent therapeutic failures reported for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infective endocarditis (IE) with vancomycin may be due to poor bactericidal activity. Alternative antibacterial approaches using bacteriophages may overcome this limitation. Objectives. An experimental rat model of MRSA IE (EE) was used to examine the efficacy of vancomycin combined with a 1:1 bacteriophage (phage) cocktail composed of Herelleviridae vB_SauH_2002 and Routreeviridae 66. Methods. Six hours after inoculation with ca. 5 log10 colony forming units (CFU) of MRSA strain AW7, animals were treated with either: (i) saline, (ii) an equimolar two-phage cocktail (bolus of 1 mL followed by a 0.3 mL\/h continuous infusion of 10 log10 plaque forming units (PFU)\/mL phage suspension), (iii) vancomycin (at a dose mimicking the kinetics in humans of 0.5 g b.i.d.), or (iv) a combination of both. Bacterial loads in vegetations, and phage loads in vegetations, liver, kidney, spleen, and blood, were measured outcomes. Results. Phage cocktail alone was unable to control the growth of strain AW7 in cardiac vegetations. However, when combined with subtherapeutic doses of vancomycin, a statistically significant decrease of \u22064.05 \u00b1 0.94 log10 CFU\/g at 24 h compared to placebo was detected (p &lt; 0.001). The administration of vancomycin was found to significantly impact on the local concentrations of phages in the vegetations and in the organs examined. Conclusions. Lytic bacteriophages as an adjunct treatment to the standard of care antibiotics could potentially improve the management of MRSA IE. Further studies are needed to investigate the impact of antibiotics on phage replication in vivo.<\/jats:p>","DOI":"10.3390\/v14081792","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T03:15:27Z","timestamp":1660706127000},"page":"1792","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Subtherapeutic Doses of Vancomycin Synergize with Bacteriophages for Treatment of Experimental Methicillin-Resistant Staphylococcus aureus Infective Endocarditis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4556-6756","authenticated-orcid":false,"given":"Jonathan","family":"Save","sequence":"first","affiliation":[{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yok-Ai","family":"Que","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, CH-3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Entenza","sequence":"additional","affiliation":[{"name":"Department of Fundamental Microbiology, University of Lausanne, CH-1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-4591","authenticated-orcid":false,"given":"Gr\u00e9gory","family":"Resch","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University of Lausanne, University of Geneva, 1211, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/nrcardio.2011.43","article-title":"Infective endocarditis","volume":"8","author":"Que","year":"2011","journal-title":"Nat. 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