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Local antimicrobial therapy is an integral aspect of treating orthopedic device‐related infection (ODRI), which is conventionally administered via polymethyl‐methacrylate (PMMA) bone cement. 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‐loaded hydrogel in a single‐stage revision for chronic methicillin‐resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single‐stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post‐mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture‐negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 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‐stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use. [ABSTRACT FROM AUTHOR]

Simple Summary: Providing adequate and prolonged pain relief to sheep undergoing invasive orthopedic surgery while keeping side effects and stress for the animals at a minimum is challenging. Transdermal patches continuously releasing the synthetic opioid fentanyl through the skin, are a frequently used method in veterinary and human medicine. To refine the current analgesia protocol, we compared the uptake of fentanyl from a transdermal fentanyl patch applied at two different skin locations in sheep. The fentanyl plasma levels were measured at different time points over five days. The patch applied on the foreleg resulted in a faster fentanyl uptake with higher peaks and a longer time within or above the target fentanyl plasma concentration when compared to the one on the thorax. Additionally, it was easier to apply the patch at the foreleg than at the thorax. Our findings suggest that the fentanyl patch should be applied to the foreleg 3–6 h before the painful insult and that its effect should last at least 48 h. When using animals in biomedical research, investigators have the responsibility to ensure adequate analgesia. Currently, transdermal fentanyl patches (TFP) are often used to provide postoperative analgesia in large laboratory animals. The aim of this study was to compare the fentanyl uptake resulting from TFP applied at two different locations, namely the foreleg and the thorax, in healthy adult sheep. Twelve sheep received a TFP with an intended dosage of 2 ug/kg/h. Blood samples were taken at different time points over a period of five days and the fentanyl plasma levels were measured. The TFP applied on the foreleg allowed a faster fentanyl uptake with higher peaks and a longer time within or above the target concentration of 0.6–1.5 ng/mL, shown to be analgesic in humans, when compared to the one on the thorax. Assuming that the effective plasma concentration described for humans is providing analgesia in sheep as well, the present findings suggest that it should be sufficient to apply the TFP 3–6 h before the painful insult and that its effect should last at least 48 h. Furthermore, when TFP are used to provide postoperative analgesia in sheep, they should be placed on the foreleg rather than on the thorax. [ABSTRACT FROM AUTHOR]