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Title: | Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates. | Authors: | Johnson P.D.R.;Roberts S.A.;Warren S.J.C.;Coombs G.W.;Tan H.-L.;Gao W.;Howden B.P.;Holmes N.E.;Turnidge J.D.;Munckhof W.J.;Robinson J.O.;Korman T. ;O'Sullivan M.V.N.;Anderson T.L. | Monash Health Department(s): | Infectious Diseases and Clinical Microbiology | Institution: | (Holmes, Gao, Johnson, Howden) Austin Centre for Infection Research, Department of Infectious Diseases, Austin Health, Heidelberg, VIC, Australia (Holmes, Johnson) Department of Medicine, University of Melbourne, Parkville, VIC, Australia (Turnidge) SA Pathology, Women's and Children's Hospital, North Adelaide, SA, Australia (Turnidge) Department of Paediatrics, Pathology and Molecular and Biomedical Science, University of Adelaide, Adelaide, SA, Australia (Munckhof) Infection Management Services, Princess Alexandra Hospital, Woolloongabba, QLD, Australia (Munckhof) Department of Medicine, University of Queensland, St. Lucia, QLD, Australia (Robinson, Coombs, Tan) Department of Microbiology and Infectious Diseases, PathWest Laboratory Medicine-WA, Royal Perth Hospital, Perth, WA, Australia (Robinson, Coombs, Tan) Australian Collaborating Ctr. for Enterococcus and Staphylococcus Species (ACCESS) Typing and Res., School of Biomedical Sciences, Curtin University, Perth, WA, Australia (Korman) Department of Infectious Diseases, Monash Health, Clayton, VIC, Australia (Korman) Department of Medicine, Monash University, Clayton, VIC, Australia (O'Sullivan) Centre for Infectious Diseases and Microbiology, Westmead Hospital, Westmead, NSW, Australia (O'Sullivan) Department of Medicine, University of Sydney, Sydney, NSW, Australia (Anderson, Warren) Department of Infectious Diseases, Royal Hobart Hospital, Hobart, TAS, Australia (Anderson, Warren) Department of Medicine, University of Tasmania, Hobart, TAS, Australia (Roberts) Auckland District Health Board, Auckland, New Zealand (Gao, Howden) Department of Microbiology, Austin Health, Heidelberg, VIC, Australia (Johnson, Howden) Department of Microbiology, Monash University, Clayton, VIC, Australia (Howden) Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Parkville, VIC, Australia | Issue Date: | 9-Sep-2014 | Copyright year: | 2014 | Publication information: | Journal of Clinical Microbiology. 52 (9) (pp 3384-3393), 2014. Date of Publication: September 2014. | Abstract: | An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes. Copyright © 2014, American Society for Microbiology. All Rights Reserved. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1128/JCM.01320-14 | Link to associated publication: | Click here for full text options | PubMed URL: | 25031442 [http://www.ncbi.nlm.nih.gov/pubmed/?term=25031442] | ISSN: | 0095-1137 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/41659 | Type: | Article | Subjects: | bacterial capsule bacterial virulence bacterium isolate clone controlled study DNA microarray epsilometer test female gene gene frequency gene function gene locus gene structure genetic analysis male *methicillin resistant Staphylococcus aureus *methicillin susceptible Staphylococcus aureus *minimum inhibitory concentration nonhuman phenotype phylogeny priority journal prognosis regulator gene *staphylococcal bacteremia *vancomycin accessory gene regulator arginine catabolic mobile element blaZ gene clfA gene sea gene spla gene human adult aged article epsilometer test female gene gene frequency gene function gene locus gene structure genetic analysis human male *methicillin resistant Staphylococcus aureus *methicillin susceptible Staphylococcus aureus *minimum inhibitory concentration nonhuman phenotype phylogeny priority journal prognosis aged *staphylococcal bacteremia adult regulator gene article bacterial capsule bacterial virulence bacterium isolate clone controlled study DNA microarray |
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