Recurrent Cases of Periprosthetic Joint Infection Caused by Staphylococcus Aureus: Reinfection or Reactivation of a Pathogen?

Background. Staphylococcus aureus is one of the most common pathogens causing periprosthetic joint infection (PJI). Despite the high genetic diversity of S. aureus strains, determining phylogenetic relationships and, consequently, the source of infection is a challenging task that can only be addressed through detailed comparison of the genomes of the obtained isolates. The aim of the study was to assess the feasibility of differentiating the cases of nosocomial periprosthetic joint infections, using whole-genome sequencing to identify genetic and phenotypic differences between isolates with the prospect of the application of evidence-based treatment strategies. Methods. Genomes of 20 S. aureus isolates from 13 patients with PJI were sequenced. Standard microbiological tests and in silico analysis of genomes using ResFinder, KmerFinder, spaTyper, and SCCmecFinder programs were employed. Results. Phylogenetic analysis was performed using core genome reconstruction and identified potential cases of nosocomial infections, as well as cases of recurrent infections. The relatedness of isolates collected between 2012 and 2019 was demonstrated, along with the evolution of their genomes, including the acquisition and loss of antibiotic resistance genes. In one case of recurrent infection, the loss of several genes was observed over a remission period of approximately 5 years. Comparison of phenotypic testing results using the disk diffusion method and resistance predictions based on genome analysis revealed discrepancies for three isolates containing the aac(6’)-aph(2’’) gene, which were resistant to tobramycin and gentamicin but susceptible to amikacin. Based on the treatment outcomes of several recurrent PJI cases, it was hypothesized that radical treatment might be more effective in cases of infections caused by multidrug-resistant nosocomial strains. Conclusions. Whole-genome sequencing enables the identification of phylogenetically related isolates, with shared genetic and phenotypic properties confirming their relatedness. Against the backdrop of high-dose antibiotic therapy, S. aureus genomes accumulate changes that, through molecular genetic testing, may help to justify the choice of radical treatment strategy for periprosthetic joint infection, such as prosthesis removal.