Can antimicrobial peptides provide an improved antimicrobial strategy for treatment of prosthetic joint infection?

With increasing antibiotic resistance and the paucity of new antibiotics in the development pipeline, exploration of antimicrobial peptide applications alone or in combination with existing antibiotics is more crucial than ever. The recent study by J. Varin-Simon, E. F. Haney, M. Colin, F. Velard, et al. (Microbiol Spectr 13:e02523-24, 2025, https://doi.org/10.1128/spectrum.02523-24), investigated the use of synthetic D-amino acid host defense peptides (HDP) to mitigate -mediated anaerobic prosthetic joint infections (PJIs). Two of the synthetic HDPs, DJK5 and AB009-D, inhibited planktonic and adherence to abiotic surfaces, while AB101-D exhibited antibiofilm activity. Moreover, co-administration of some HDPs with antibiotics showed slight reductions in antibiotic MIC. Finally, the D-amino acid HDPs AB009-D and AB101-D significantly reduced osteoblast internalization of potentially via bactericidal activity prior to internalization. Further studies are needed to develop multi-faceted, innovative antimicrobial strategies to prevent and treat PJIs with broader impact on antimicrobial control in health and industry.