Vancomycin and phage COP-80B combination therapy for Staphylococcus epidermidis periprosthetic joint infections : a preclinical mouse study

Štilec, Vida (author), Marušić, Monika (author), Motaln, Helena (author), Gregorič, Klara (author), Draksler, Urška (author), Čater, Maša (author), Izlakar, Jani (author), Janež, Nikolaja (author), Trebše, Rihard (author), Horvat, Simon (author), Peterka, Matjaž (author)

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.

• Language: English
• Keywords: phage therapy, periprosthetic joint infection, Staphylococcus epidermidis, mice, infection models, vancomycin
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Publication date: 01.01.2026
• Year: 2026
• Number of pages: Str. 2859–2873
• Numbering: Vol. 45
• PID: 20.500.12556/RUL-189499
• UDC: 577
• ISSN on article: 1435-4373
• DOI: 10.1007/s10096-026-05561-x
• COBISS.SI-ID: 282405123
• Publication date in RUL: 08.10.2026

Record is a part of a journal

• Title: European journal of clinical microbiology & infectious diseases
• Shortened title: Eur. j. clin. microbiol. infect. dis.
• Publisher: Springer
• ISSN: 1435-4373
• COBISS.SI-ID: 512014361

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: fagna terapija, okužbe umetnih sklepov, Staphylococcus epidermidis, modeli okužb, vankomicin