Abstract
Aim
Staphylococcus epidermidis has emerged as an important opportunistic pathogen causing orthopedic device-related infections (ODRIs). In this prospective clinical and laboratory study, we have investigated the association of genome variation and phenotypic features of the infecting S. epidermidis isolate with the clinical outcome of the infected patient.
Method
One hundred and four invasive S. epidermidis isolates were prospectively collected from patients with ODRI. Upon patient entry into the study, surgical parameters such as type of implant; open or closed fracture were documented. Personal characteristics were also documented and included: gender; age; body mass index (BMI); smoker/non-smoker; overall medical condition (Charlson comorbidity index); and chronic immunosuppressive conditions. Any revision surgeries involving the site of interest and all isolated pathogens were recorded throughout the course of treatment and follow-up. The clinical outcome after treatment was measured with a mean follow-up period (FUP) of 26 months, and each patient was then considered to have been “cured” or “not cured”. The isolates were tested for their antibiotic susceptibility and ability to form biofilm. Whole genome sequencing was performed on all isolates and genomic variation was related to features associated with “cured” and “not cured”.
Results
Strong biofilm formation and resistance to aminoglycoside antibiotics were associated with a “not cured” treatment outcome (p = 0.031 and p < 0.001, respectively). Isolates within the “not cured” group were more prevalent in the phylogenetic clade B compared to the predominant clade A (p = 0.08). Based on a gene-by-gene analysis, some accessory genes were more prevalent in isolates from patients that were “not cured”. These included: the biofilm-associated bhp gene; the antiseptic resistance qacA gene, the cassette chromosome recombinase encoding genes ccrA and ccrB and IS256-like transposase.
Conclusions
The novelty of this study was that all S. epidermidis isolates were whole genome sequenced in order to screen for features associated with poor clinical outcome. Multiple factors were found to have an influence on poorer patient clinical outcome, such as multiple revisions surgeries, biofilm formation and antibiotic resistance to aminoglycosides emphasizing the multifactorial pathogenesis of ODRI. Furthermore, poor treatment outcome was associated with a small number of mobile elements that could potentially be used as prognostic markers for ODRI treatment outcome.
