Antibiotic resistance in chronic biofilm infections - Novel mechanisms and approaches to the diagnosis and treatment of periprosthetic joint infections

The project is funded by CARe (Transmission), the Region Västra Götaland and the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754412 (MoRE2020), LUA-ALF (ALFGBG-719961), the Handlanden Hjalmar Svensson Foundation, the Adlerbertska Foundation, the Doctor Felix Neubergh Foundation, and the Göteborgs Medical Society. In total the project is funded with 2,52 MSEK.

This clinical scientific research is conducted in the Gothenburg area, and includes international collaboration. The principle researchers are: The Sahlgrenska Academy at University of Gothenburg (Department of Biomaterials): Margarita Trobos (Principle Investigator), Magdalena Zaborowska, Maria Hoffman; The Sahlgrenska University Hospital (Department of Orthopaedics, and the Swedish Hip Arthroplasty Register): Ola Rolfson (PI), Karin Svensson, (Department of Infectious Diseases): Jonatan Tilllander, (Department of Clinical Microbiology): Bodil Jönsson; and The Public University of Navarre (Spain) (Department of Bacterial Pathogenesis): Iñigo Lasa.

This project addresses two major threats to global health: antibiotic resistance and chronic biofilm infections, with consequences in patient mortality and healthcare costs. Treatment with orthopaedic implants such as hip and knee replacements has improved quality of life for many patients. According to the Swedish Hip and Knee Arthroplasty registries 21,000 primary total hip replacements and 14,000 primary total knee replacements are performed in Sweden annually. Periprosthetic joint infection (PJI) is a feared complication in joint replacement surgery and incidences of 0.57%-1.55% have been reported. Medical implants are highly susceptible to bacterial biofilm formation making bacteria resistant to the immune system and antibiotics.

The aims of this study are: (1) To evaluate a diagnostic tool for determining the relevant antibiotic concentrations needed for the treatment of biofilm-related periprosthetic joint infection, and (2) To determine the function and mechanisms of staphylococcal extracellular vesicles (EVs) in the antimicrobial resistance of biofilm infections.

This is a clinical retrospective study where the medical records of patients diagnosed with first time infection (117 hip patients and 63 knee patients) will be reviewed and several clinical parameters evaluated. A total of 113 staphylococci isolated from PJI will be characterized by their biofilm formation ability, biofilm susceptibility, and genetic carriage of virulence factors.
To evaluate vesicle formation under stress conditions, EVs will be isolated from Staphylococcus spp. in the presence of subinhibitory concentrations of antibiotics. EV-mediated antimicrobial protection assays, and molecular investigations of vesicle-mediated cell-cell communication in biofilms of clinical strains will be carried out. The molecular content of EVs will be characterized and transformation-like experiments will be performed.

This project will generate crucial understanding of the persistence and antimicrobial resistance of chronic biofilm infections. In addition, this project may provide a reproducible, low cost, and time-efficient diagnostic tool for determining the relevant concentrations of antibiotics needed for the treatment of biofilm-related infections within prosthetic surgery.

Publication in 2016:
Zaborowska M, Tillander J, Branemark R, Hagberg L, Thomsen P, Trobos M. Biofilm formation and antimicrobial susceptibility of staphylococci and enterococci from osteomyelitis associated with percutaneous orthopaedic implants. J Biomed Mater Res B Appl Biomater. Oct 25 2016.