Do All Prosthetic Joint Infection Clinical Isolates Form Aggregates in Synovial Fluid That Are Resistant to Antibiotic Agents?

Background: Chronic prosthetic joint infections (PJI) are associated with substantial morbidity because conventional antibiotic agents lack activity to bacteria in biofilms that necessitates prosthetic removal to attempt definitive cure. However, these are complex infections that go beyond biofilms and bacteria can be present in various other different states such as synovial fluid aggregates. Consequently, the purpose of this study was to assess the propensity of historically preserved PJI clinical isolates to form synovial fluid aggregates and if aggregation occurred then what is proclivity to be tolerant to high doses of antibiotic agents. Patients and Methods: Historically preserved chronic PJI clinical isolates from 2021 were evaluated for their ability to form synovial fluid aggregates under static and dynamic conditions in 24-microwell plates. Tolerance to vancomycin, gentamicin, or amphotericin was conducted by adding high concentrations of these antibiotic agents to synovial fluid microbial aggregates. Results: All clinical isolates formed synovial fluid aggregates under dynamic conditions, which with the use of scanning electron microscopy showed dense collections of bacteria with synovial fluid polymers. However, under static conditions only Staphylococcus aureus formed aggregates. Importantly, all the microbes in these aggregates were tolerant to high concentrations of antibiotic agents. Conclusions: This study demonstrates that synovial fluid aggregation occurred with all bacterial and fungal species assessed. Therefore, the findings here have important clinical ramifications given the extent that this phenomenon occurs across microbial species and the propensity for the microbes in these aggregates to be tolerant to antibiotic agents.