Luca-Quirin Herrmann

Introduction: Periprosthetic joint infection (PJI) is a serious, potentially chronic, complication following joint replacement surgery. Because PJI is mainly driven by the formation of biofilm, it is critical to administer effective antibiotic treatments during the early stages of the infection to avoid persistence. Fosfomycin in combination with rifampicin (FR) has been increasingly highlighted as an effective treatment against especially Gram-positive PJI. The goal of this study is to evaluate the effectiveness of FR in a dynamic biofilm model and compare it to currently used antibiotic regimens for PJI. It is hypothesized that FR treatment represents a competent alternative to existing combination therapies for PJI.
Methods: FR was compared to combinations of cotrimoxazole, clindamycin, or levofloxacin in combination with rifampicin by analyzing their minimum biofilm eradication concentration (MBEC), defined as a 99.9% reduction in viable bacterial growth, against S. aureus ATCC25923 using the Calgary Biofilm Device (CBD). All MBECs of the combination therapies were further investigated in the CDC bioreactor. Viable bacterial growth was quantified mechanically using log-reduction assessments.
Results: MBEC of fosfomycin in combination with rifampicin shows the highest efficacy (0.03mg/L), followed by the combinations with cotrimoxazole (0.125mg/L), clindamycin (0.25mg/L), and levofloxacin (1mg/L). When applying the obtained MBEC values to the dynamic bioreactor model, FR showed a significantly higher average reduction in biofilm compared to the cotrimoxazole combination (98.4% vs. 96.1%, p=0.0076).
Conclusion: The combination of fosfomycin with rifampicin seems promising, representing both the most efficient MBEC and the highest reduction in biofilm in the bioreactor model when compared to currently used combination regimens. Considering fosfomycin’s low toxicity and flexible administration route, FR could offer an efficient alternative to currently used regimens when treating PJI. To further validate these findings, future research should focus on testing clinical isolates that are associated with early PJI biofilms.