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

Abstract

Prosthetic joint infection (PJI) is a feared and challenging to diagnose complication after arthroplasty, with Staphylococcus epidermidis as the major pathogen. One important criteria to define PJI is the detection of phenotypically indistinguishable microorganisms with identical antibiotic susceptibility pattern in at least two different samples. However, owing to phenotypical variation within genetic clones and clonal variation within a phenotype, the criteria may be ambiguous. We investigated the extent of diversity among coagulase-negative staphylococci (CoNS) in PJI and characterised S. epidermidis isolates from PJI samples, specifically multiple S. epidermidis isolates identified in individual PJI patients. We performed a retrospective cohort study on 62 consecutive patients with PJI caused by CoNS from two hospitals in Northern Sweden. In 16/62 (26%) PJIs, multiple S. epidermidis isolates were available for whole-genome analyses. Hospital-adapted multidrug-resistant genetic clones of S. epidermidis were identified in samples from 40/62 (65%) of the patients using a combination of pulsed-field gel electrophoresis and multilocus sequence typing. Whole-genome sequencing showed the presence of multiple sequence types (STs) in 7/16 (44%) PJIs where multiple S. epidermidis isolates were available. Within-patient phenotypical variation in the antibiotic susceptibility and/or whole-genome antibiotic resistance gene content was frequent (11/16, 69%) among isolates with the same ST. The results highlight the ambiguity of S. epidermidis phenotypic characterisation as a diagnostic method in PJI and call for larger systematic studies for determining the frequency of CoNS diversity in PJIs, the implications of such diversity for microbiological diagnostics, and the therapeutic outcomes in patients.

Patient-related factors associated with superficial surgical site infection and progression to a periprosthetic joint infection after elective primary total joint arthroplasty: a single-centre, retrospective study in Sweden

“…Cultures of a superficial infection can be misleading, which can be classified as contamination, even if a possibility of a clinical significance of skin flora found in cultures has recently been reported. 40 …”

“…Another limitation is that SSSI is not culture-verified but determined by a consultant orthopaedic surgeon that reflects the clinical reality. Cultures of a superficial infection can be misleading, which can be classified as contamination, even if a possibility of a clinical significance of skin flora found in cultures has recently been reported 40…”

“…Cultures of a superficial infection can be misleading, which can be classified as contamination, even if a possibility of a clinical significance of skin flora found in cultures has recently been reported. 40 As in infection-related research in general, where a small number of infections are a major challenge, this study may have failed to detect an association between a potential risk factor and postoperative infection due to a type 2 error.…”

Emerging resistance inStaphylococcus epidermidisduring dalbavancin exposure: a case report andin vitroanalysis of isolates from prosthetic joint infections

“…We also observed other genetic variability between these closely related isolates, similar to a recent study in heterogeneity in S. epidermidis PJIs. 38 These differences include a likely acquisition of other resistance markers that could indicate the selection pressure under which these isolates thrived.…”

Microbiological Profiles of Patients with Periprosthetic Joint Infection of the Hip or Knee

“…In this context, Widerström et al tried to evaluate the heterogeneity of S. epidermidis in PJI with the help of whole-genome sequencing. Their main finding was, that even S. epidermidis isolates taken only from patients with confirmed PJI displayed an astonishingly high ambiguity [ 18 ]. Although they were not able to distinguish between contamination and detection of the causative pathogen with whole-genome sequencing, they suggested that detection of S. epidermidis in more than one culture with identical results of the antibiotic susceptibility testing makes a contamination less likely.…”