Antimicrobial-laden PerOssal beads display in vitro inhibition and killing of extensively drug-resistant Gram-negative bacteria associated with conflict wounds in Ukraine

Aims: Open fractures sustained in contemporary conflict are associated with high-energy transfer, contamination with resistant bacteria, and delays to surgical care, resulting in high rates of infection. Similar conditions occur in civilian disasters, where crush injuries and overwhelmed healthcare systems prolong the interval to surgical wound excision. Prophylactic systemic antimicrobial regimens may be ineffective due to antimicrobial resistance or limited bioavailability in bone and joint tissues. Local antimicrobial delivery can provide higher drug concentrations within the wound, which may be sufficient to overcome resistance. This route is established in bone and joint infection, although evidence in conflict trauma is lacking. We evaluated the in vitro activity of antimicrobial-laden PerOssal hydroxyapatite and calcium sulphate beads. Methods: . The antimicrobial effects of antimicrobial-laden PerOssal beads were assessed by zone-of-inhibition testing and time-kill analysis. Results: All Gram-negative isolates from Ukraine were resistant to gentamicin, tobramycin, co-amoxiclav, cefazolin, and ciprofloxacin, with minimum inhibitory concentrations (MICs) exceeding European Committee on Animicrobial Susceptibility Testing (EUCAST) breakpoints. PerOssal beads laden with gentamicin, tobramycin, or cefazolin were weakly growth inhibitory. However, gentamicin-rifampicin in combination achieved consistent broad-spectrum bacterial inhibition and killing, while co-amoxiclav-loaded beads inhibited the growth of all bacterial strains. Conclusion: Antimicrobial-laden PerOssal hydroxyapatite and calcium sulphate beads displayed in vitro inhibition and killing of XDR Gram-negative bacteria associated with contaminated traumatic wounds. Early local antimicrobial delivery may reduce infection risk following heavily contaminated open fractures, particularly when surgical wound excision is delayed. This may be relevant to both modern conflict and civilian disaster settings. Further work is required to determine the effectiveness of this approach in vivo.