Projects / Programmes source: ARIS

Development of bacteriophage treatment against antibiotic resistant bacteria in orthopaedic implant related infections

Research activity

Code Science Field Subfield
3.01.00  Medical sciences  Microbiology and immunology   

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
antibiotic resistance, orthopeadic implants, bacteriophages, Staphylococcus epidermidis
Evaluation (rules)
source: COBISS
Researchers (18)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  54374  PhD Urban Bezeljak  Biochemistry and molecular biology  Researcher  2021  14 
2.  52971  Tina Brecelj  Biotechnology  Researcher  2020 - 2022 
3.  11308  PhD Andrej Cör  Oncology  Researcher  2020 - 2023  403 
4.  33148  PhD Maša Čater  Biotechnology  Technical associate  2022 - 2023  103 
5.  53966  Klara Gregorič  Biotechnology  Researcher  2020 
6.  10412  PhD Simon Horvat  Biotechnical sciences  Researcher  2020 - 2023  548 
7.  30700  PhD Rosana Hudej  Biotechnology  Researcher  2021 - 2023  26 
8.  35241  Hana Jug  Biotechnology  Researcher  2020 - 2023 
9.  35145  Maja Leskovec  Biotechnology  Researcher  2020 - 2023  13 
10.  33035  PhD Rene Mihalič  Neurobiology  Researcher  2020 - 2023  110 
11.  16327  PhD Matjaž Peterka  Biotechnology  Head  2020 - 2023  218 
12.  51857  Neža Pogorevc  Animal production  Researcher  2022 - 2023  32 
13.  38858  Katja Skulj    Technical associate  2020 - 2023  14 
14.  56353  Vida Štilec  Biotechnology  Researcher  2022 - 2023  13 
15.  35429  PhD Katja Šuster  Neurobiology  Researcher  2020 - 2023  30 
16.  23524  PhD Rihard Trebše  Neurobiology  Researcher  2020 - 2023  408 
17.  37945  Jasmina Tušar  Biochemistry and molecular biology  Researcher  2020 - 2021 
18.  23594  PhD Jana Vidič  Materials science and technology  Researcher  2020 - 2023  65 
Organisations (4)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0355  Orthopaedic Hospital Valdoltra  Ankaran  5053765  2,306 
2.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  65,885 
3.  1655  Sartorius BIA Separations L.t.d., Separations technology company  Ajdovščina  1319612  1,179 
4.  3030  Center of Excellence for Biosensors, Instrumentation and process Control  Ajdovščina  3660460  935 
Joint replacement surgery is increasingly performed as a result of increasing life expectancy, improvements in surgical techniques, and the increased rates of obesity. Prosthetic joint infection (PJI) is a possible post-operative complication and its rate has remained steady throughout the years, at 1.4–3.3%, depending on the joint being replaced. A majority of PJIs are caused by staphylococci (>50%), streptococci, enterococci, aerobic gram-negative bacilli, and anaerobic bacteria with leading Cutibacterium acnes. Once in contact with the surface of the implant, the microorganisms colonize it and form bacterial biofilms, which complicate treatment. Bacterial biofilms are associated with significantly decreased antimicrobial susceptibility. Bacteria in biofilms grow slowly, which makes growth dependent antimicrobials particularly ineffective. In addition, implant sites are often poorly vascularized which decreases the ability of antimicrobial agents to reach the site of biofilms, while also impeding host defences. Treatment of prosthetic joint infection can be time-consuming, expensive and arduous. Various therapies have been used, including surgical removal of all the infected tissue and implant, and a combination of débridement with implant retention and long-term antimicrobial therapy that is active against biofilm microorganisms. Ideally, the antimicrobial agent for treatment of PJI should have bactericidal activity against surface-adhering, slow-growing, and biofilm-producing microorganisms. Such effect is typically achieved with combination of antibiotics. Increased antibiotic resistance of bacteria causing PJI, biofilm barrier and long term treatments dictate a need for further optimization of antibacterial therapy which could result in more implant retention in chronic infections, thus reducing the increased morbidity and delayed return to function associated with the two stage exchange. Bacteriophages, viruses that specifically recognize and lyse bacteria are promising candidates for antibacterial therapy. In comparison with antibiotics, they specifically target a bacterium, have a minimal effect on normal microbiota, and amplify themselves on the site of infection. There are already some sporadic applications of bacteriophage therapy for treatment of PJI but to demonstrate efficacy and safety systematic, FDA and EMA compliant approach is needed. Therefore, the project will evaluate bacteriophage efficacy against staphylococci in PJI in mice model and address issues not being evaluated until today: mode of application (systemic vs local), bacteriophage distribution in the animal body (basic bacteriophage pharmacokinetics) and development of bacteria resistance against bacteriophages. COBIK, a leading project partner, has an extensive collection of different clinically relevant bacteria isolated from PJI, and bacteriophages, specific for these bacteria. COBIK has already demonstrated bacteriophage efficacy in vitro on cell culture model and in order to proceed towards clinical application needed by Orthopaedic hospital Valdoltra patients, we need to test bacteriophage efficacy on the mice model, mastered by Centre for Laboratory animals. Bacteriophage formulation will be produced and formulated by technology developed by BIA Separations. The main goal of the project is to evaluate efficacy of bacteriophage treatment against Staphylococcus epidermidis in orthopaedic implant related infections in mice model. In the frame of the project we will: · prepare and evaluate in vitro efficacy of an innovative bacteriophage formulation · optimize bacteriophage GMP-like manufacturing process · determine bacteriophage distribution in mice organs after systemic and local application · evaluate bacteriophage treatment efficacy in mice model · evaluate combined antibiotic and bacteriophage treatment efficacy in mice model · determine bacteria resistance development against bacteriophages after bacteriophage therapy.
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