Experimental Validation of Antimicrobial Drug Combinations for Bone Cement Impregnation

Background. The implantation of an antimicrobial spacer is widely used in the comprehensive treatment of periprosthetic joint infection (PJI). Most commonly, bone cement is additionally impregnated with vancomycin, which is active only against Gram-positive bacteria. However, there is a global increase in Gram-negative bacterial resistance to most antibiotics, necessitating the development of new approaches to overcome this resistance, including in the context of local antibacterial therapy. The aim of the study was to determine the duration of antimicrobial activity and the mechanical properties of gentamicin-containing bone cement samples additionally impregnated with the combinations of highly dispersed silver (HD-Ag) and various antibiotics. Methods. Control samples were prepared using the commercial polymethylmethacrylate-based bone cement DePuy CMW 3 Gentamicin (DePuy Synthes), which contains 4.22% gentamicin. Additionally, six experimental samples with different combinations of antimicrobial agents were prepared and tested. Antimicrobial activity (AMA) was assessed against S. aureus (MSSA, MRSA), K. pneumoniae, and P. aeruginosa. The mechanical properties of the most effective samples were evaluated in comparison with the control samples. Statistical analysis was performed using the Past 4 software system. Results. The control samples of commercial bone cement demonstrated the shortest duration of activity against MSSA (7 days) and showed no activity against MRSA or Gram-negative bacteria. The addition of 10 wt% fosfomycin and HD-Ag to the bone cement (BC 1) tripled the AMA duration against MSSA, K. pneumoniae, and P. aeruginosa. The addition of 5 wt% vancomycin to BC 1 (BC 2) extended the AMA duration against Gram-negative bacteria to 14-16 days and against Staphylococcus spp. to 4 weeks. The highest activity against Gram-negative bacteria was observed in samples containing HD-Ag and 10 wt% aztreonam (BC 5 and BC 6), whose mechanical properties did not significantly differ from the control samples. Conclusion. Combinations containing HD-Ag, vancomycin, fosfomycin, and aztreonam demonstrated prolonged antimicrobial activity. This may improve the effectiveness of the debridement stage in two-stage revision arthroplasty for hip periprosthetic joint infection, making these combinations promising for clinical application.