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PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic\u2010loaded hydrogel in a single\u2010stage revision for chronic methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single\u2010stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (<jats:italic>n<\/jats:italic>\u2009=\u20095 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration,\u00a0renal and liver function tests,\u00a0and quantitative microbiology on tissues and hardware post\u2010mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (<jats:italic>p<\/jats:italic>\u2009=\u20090.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture\u2010negative. Antibiotic delivery via hydrogel resulted in 10\u2013100 times greater local concentrations for the first 2\u20133 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single\u2010stage revision with hydrogel or PMMA is\u00a0equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.<\/jats:p>","DOI":"10.1002\/jor.24949","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T13:09:35Z","timestamp":1607692175000},"page":"438-448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Single\u2010stage revision of MRSA orthopedic device\u2010related infection in sheep with an antibiotic\u2010loaded hydrogel"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1191-3916","authenticated-orcid":false,"given":"Andrew L.","family":"Foster","sequence":"first","affiliation":[{"name":"AO Research Institute Davos  Davos Switzerland"},{"name":"Queensland University of Technology (QUT) Faculty of Science and Engineering  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