20.500.12556/RUL-189499 Vancomycin and phage COP-80B combination therapy for Staphylococcus epidermidis periprosthetic joint infections a preclinical mouse study The increasing number of joint replacement surgeries has led to an increase in periprosthetic joint infections (PJI). Chronic PJI caused by Staphylococcus epidermidis is very common and challenging to treat, prompting interest in bacteriophage therapy. Preclinical studies are essential for optimizing phage administration routes and dosages. Here, phage replication and bacterial growth inhibition using phage and vancomycin were first assessed in vitro. Then, chronic PJI was induced in mice using biofilm-coated titanium implants inoculated with S. epidermidis COB-SE3 to evaluate the efficacy of phage COP-80B and vancomycin therapy. Mice received one intra-articular and two intraperitoneal phage doses over three days, along with vancomycin administered twice daily for five days. Four weeks after implantation, we quantified and compared bacterial loads in periarticular tissues and implants across four groups: untreated controls, phage monotherapy, vancomycin monotherapy, and phage-vancomycin combination. Infection persistence was lower than expected, limiting the ability to detect treatment effects and assess therapeutic efficacy in this low-virulence model. Intra-articular administration of 1010 PFU of COP-80B did not alter plasma alanine aminotransferase levels, indicating no hepatotoxicity. Bacterial isolates remained susceptible to both phage and vancomycin, while phage-neutralizing antibodies developed during treatment. Overall, this study evaluates phage-vancomycin therapy while also contributing a murine model that advances methodological development for chronic S. epidermidis PJI research, with additional refinement of infection kinetics needed to reliably assess therapeutic efficacy. phage therapy periprosthetic joint infection Staphylococcus epidermidis mice infection models vancomycin fagna terapija okužbe umetnih sklepov Staphylococcus epidermidis modeli okužb vankomicin true false true Angleški jezik Slovenski jezik Članek v reviji 2026-10-08 08:13:46 2026-10-08 08:13:54 2026-10-10 03:40:52 0000-00-00 00:00:00 2026 0 0 Str. 2859–2873 Vol. 45 2026 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2026-01-01 577 1435-4373 10.1007/s10096-026-05561-x 282405123 RAZ_Stilec_Vida_2026.pdf RAZ_Stilec_Vida_2026.pdf 1 66CC64D332BC39EF18AE9159314A4079 3c76e4ec6162a86efa122af88a68982d650f65b4bc1e91cd4b582088e42fdecf 6c34454c-c2df-11f1-8bc5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=250090 https://doi.org/10.1007/s10096-026-05561-x 1 4df34abd-c2df-11f1-8bc5-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=250089 Biotehniška fakulteta Medicinska fakulteta 0 0 0