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.

Highlights

  • Prosthetic joint replacement is one of the most important medical innovations of the twentieth century, and it has significantly improved the quality of life for millions of individuals worldwide by providing pain relief and restoring joint function, mobility, and independence [1, 2]

  • We investigated the diversity among coagulase-negative staphylococci (CoNS) in prosthetic joint infection (PJI) and characterised in detail the S. epidermidis isolates from these infections

  • We found considerable within-patient diversity in S. epidermidis isolates, with variations in phenotypic and genotypic resistance observed in the majority (13/16; 81%) of cases, and between isolates with the same sequence types (STs)

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Summary

Introduction

Prosthetic joint replacement is one of the most important medical innovations of the twentieth century, and it has significantly improved the quality of life for millions of individuals worldwide by providing pain relief and restoring joint function, mobility, and independence [1, 2]. Prosthetic joint infection (PJI) following joint replacement. Since phenotypic morphological variations [9], including the presence of small colony variants and different antibiograms, have been reported in monoclonal CoNS infections [10,11,12], the term ‘phenotypically identical organisms’ is ambiguous. The assessment of CoNS in clinical cultures is demanding as CoNS are a European Journal of Clinical Microbiology & Infectious Diseases ubiquitous part of the human skin microbiota and often for S. epidermidis display high sub-species heterogeneity [13, 14], which makes distinction between contamination and true infection challenging. We investigated the extent of diversity among CoNS in PJI and characterised in detail the S. epidermidis in these infections which revealed substantial within-patient diversity further highlighting the complexity and ambiguity in the current phenotypical assessment as the diagnostic criteria

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