Heterogeneity of Staphylococcus epidermidis in prosthetic joint infections: Time to reevaluate microbiological criteria?

Prosthetic joint infection (PJI) is a feared complication after arthroplasty with Staphylococcus epidermidis as a major pathogen. One diagnostic criteria for PJI diagnosis is the finding of phenotypically identical organisms based on common laboratory tests in two or more periprosthetic microbial cultures. Because of phenotypical variation within a genetic clone, and clonal variation within a phenotype, the criteria may be ambiguous. Here, we investigate the extent of diversity among coagulase-negative staphylococci in PJI and characterize in detail S. epidermidis isolates from these infections. We performed a retrospective cohort study of 62 consecutive patients with PJI caused by coagulase-negative staphylococci (CoNS) from two hospitals in Northern Sweden. From 16 of the patients, two to nine S. epidermidis isolates were available for whole-genome analyses. Hospital-adapted multidrug-resistant genetic clones of S. epidermidis were identified in 40/62 (65%) of the PJIs using a combination of analysis by pulsed-field gel electrophoresis and multiple-locus sequence typing. Whole genome sequencing showed presence of multiple sequence types (STs) in seven (7/16, 44%) PJIs. Among isolates of the same ST, within-patient phenotypical variation in antibiotic susceptibility and/or whole-genome antibiotic resistance gene content was frequent (11/16, 69%). These results highlight the ambiguity of using phenotypical characterization of S. epidermidis as diagnostic criteria in PJI. The results call for larger systematic studies to determine the frequency of CoNS diversity in PJIs, the implications of such diversity for microbiological diagnostics, and for the therapeutic outcome in patients.