title: Reduced pro-inflammatory responses to Staphylococcus aureus bloodstream infection and low prevalence of enterotoxin genes in isolates from patients on haemodialysis.
abstract: Patients with end-stage renal failure undergo regular haemodialysis (HD) and often develop episodes of Staphylococcus aureus bloodstream infection (BSI), which can re-occur. However, clinically, patients on HD, with S. aureus BSI, respond well to treatment, rarely developing overt signs of sepsis. We investigated the contributions of bacterial virulence and cytokine responses to the clinical course of S. aureus BSI in HD and non-HD patients. Seventy patients were recruited, including 27 (38.6 %) patients on HD. Isolates were spa-typed and virulence and antimicrobial resistance gene carriage was investigated using DNA microarray analysis. Four inflammatory cytokines, IL-6, RANTES, GROγ and leptin, were measured in patient plasma on the day of diagnosis and after 7 days. There was no significant difference in the prevalence of genotypes or antimicrobial resistance genes in S. aureus isolates from HD compared to non-HD patients. The enterotoxin gene cluster (containing staphylococcal enterotoxins seg, sei, sem, sen, seo and seu) was significantly less prevalent among BSI isolates from HD patients compared to non-HD patients. Comparing inflammatory cytokine response to S. aureus BSI in HD patients to non-HD patients, IL-6 and GROγ were significantly lower (p = 0.021 and p = 0.001, respectively) in HD patients compared to other patients on the day of diagnosis and RANTES levels were significantly lower (p = 0.025) in HD patients on day 7 following diagnosis. Lowered cytokine responses in HD patients and a reduced potential for super-antigen production by infecting isolates may partly explain the favourable clinical responses to episodes of S. aureus BSI in HD patients that we noted clinically.
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Smurfit Building, Dublin 9, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: McNicholas
authors.affiliation: Department of Microbiology, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: A
authors.initials: A
authors.lastname: Fe Talento
authors.affiliation: Department of Microbiology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: O'Gorman
authors.affiliation: Department of Microbiology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: M M
authors.initials: MM
authors.lastname: Hannan
authors.affiliation: Department of Microbiology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: C M
authors.initials: CM
authors.lastname: Greene
authors.affiliation: Department of Nephrology, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: P J
authors.initials: PJ
authors.lastname: Conlon
authors.affiliation: Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland.
authors.forename: A C
authors.initials: AC
authors.lastname: Shore
authors.affiliation: Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Lincoln Place, Dublin 2, Ireland.
authors.forename: D C
authors.initials: DC
authors.lastname: Coleman
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Smurfit Building, Dublin 9, Ireland.|Department of Microbiology, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: H
authors.initials: H
authors.lastname: Humphreys
authors.affiliation: Department of Clinical Microbiology, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Smurfit Building, Dublin 9, Ireland. dfitzgeraldhughes@rcsi.ie.
authors.forename: D
authors.identifier: http://orcid.org/0000-0002-4843-3839
authors.initials: D
authors.lastname: Fitzgerald-Hughes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000382:microbiology / Q000473:pathology*; D016207:Cytokines / Q000097:blood*; D004768:Enterotoxins / Q000235:genetics*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D046228:Microarray Analysis; D008826:Microbial Sensitivity Tests; D058889:Molecular Typing; D020411:Oligonucleotide Array Sequence Analysis; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D013203:Staphylococcal Infections / Q000382:microbiology / Q000473:pathology*; D013205:Staphylococcal Protein A / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D037521:Virulence Factors / Q000235:genetics
chemical_list: D016207:Cytokines; D004768:Enterotoxins; D013205:Staphylococcal Protein A; D037521:Virulence Factors