Bacterial skin colonization with a specific Cutibacterium avidum clade as a risk factor for periprosthetic joint infections-a multicenter study.

Cutibacterium avidum is increasingly recognized as a causative agent of periprosthetic joint infections (PJIs), yet data on its pathogenic potential and distinguishing features from commensal strains remain limited. In this multicenter study, we compared 11 C. avidum isolates from PJIs with 32 isolates from healthy skin collected across four European hospitals. We investigated phylogenetic relationships, antibiotic susceptibility, biofilm formation, and bacterial fitness. Phylogenomic analysis revealed two main clades within the C. avidum population. All PJI isolates belonged exclusively to Clade 1, which also included skin isolates. Within Clade 1, gene content analysis showed no consistent genetic differences between PJI and skin isolates. All isolates exhibited moderate to strong biofilm formation, with no significant differences in either data set. Minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC) values were low and largely concordant, while minimal biofilm eradication concentration (MBEC) values were elevated for all antibiotics except rifampin. One isolate was resistant to clindamycin due to the erm(X) gene. Rifampin consistently showed the lowest MIC, minimal bactericidal concentration, MBIC, and MBEC values. Bacterial fitness, assessed via bacterial quantitative fitness analysis, was significantly lower in PJI isolates compared to skin isolates when all strains were analyzed (P = 0.039), but this difference was not statistically significant when restricted to Clade 1. In conclusion, C. avidum isolates are strong biofilm producers irrespective of clinical origin. PJI isolates are restricted to a single phylogenetic clade, yet lack distinct biofilm or fitness traits within that clade, suggesting that multiple Clade 1 strains may have the potential to cause PJIs.IMPORTANCECutibacterium avidum has long been considered a skin commensal, but it is increasingly associated with prosthetic joint infections (PJIs). Despite its clinical emergence, little is known about its virulence potential or how invasive strains differ from commensal ones. This multicenter study provides the most comprehensive comparative analysis to date, integrating phenotypic and genomic data from both PJI-associated and skin-derived isolates. We show that all isolates are strong biofilm formers and that invasive isolates exhibit reduced growth fitness-a phenotype linked to persistence and treatment failure in other pathogens. Notably, all PJI isolates belonged to a single phylogenetic clade, suggesting that specific lineages of C. avidum may be more likely to cause infection. These findings help clarify the biology of this emerging pathogen and provide a foundation for improved diagnostics, susceptibility testing, and future infection prevention and treatment strategies.