Molecular Epidemiology Determinants of Invasive S. Epidermidis in Cancer Patients

Background: Staphylococcus epidermidis is a leading cause healthcare associated bacterial bloodstream infections, and S. epidermidis strains are often resistant to a broad array of antibiotics. To date, molecular epidemiology and antimicrobial resistance studies of S. epidermidis have utilized convenience samples without regard to whether the isolate, which is a ubiquitous human commensal, had actually caused an invasive infection.

Methods: Illumina MiSeq based whole genome sequencing was performed on 53 unique S. epidermidis strains that had caused a definite bloodstream infection as defined by CDC criteria. Multi-locus sequence types (ST) were determined and subsequent Eburst analysis was used to place STs into clonal complexes (CC). Antimicrobial resistance elements were identified using RESFINDER. Clinical data was abstracted from the electronic medical record including type of malignancy, neutrophil count, organism density defined by colony forming units (CFUs)) and presence or absence of prolonged bacteremia (defined as ≥ 2 sets of blood cultures positive > 24 hours apart).

Results: A total of 17 distinct STs were identified with the largest number of isolates being ST-5 (n =15) and ST-2 (n=10). Three major clonal complexes were identified (CC-2, CC-5 and CC-6). Compared to non-CC-2 strains, CC-2 isolates had a significantly higher CFU bloodstream density (P = 0.03). Conversely, CC-5 strains were more likely to cause prolonged bacteremia compared to non-CC-5 strains (P = 0.04). Prominent antimicrobial resistance elements included the macrolide resistance encoding gene erm(C) (28 isolates), the β-lactam resistance determinant mecA (41 isolates), and the tetracycline resistance element tet(K) (17 isolates). Additionally, the cfr gene which encodes for a linezolid resistance element was detected in two strains.

Conclusion: This is the first study to use whole genome sequencing to determine the molecular epidemiology and antimicrobial resistance determinants of S. epidermidis strains that have caused definite invasive infection. We identified clusters of strains that are associated with adverse clinical outcomes and have defined the genetic basis for a wide array of antimicrobial resistance.