Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates

N.E. Holmes; J.D. Turnidge; W.J. Munckhof; J.O. Robinson; T.M. Korman; M.V.N. O'Sullivan; T.L. Anderson; S.A. Roberts; S.J.C. Warren; G.W. Coombs; H-L Tan; W. Gao; P.D.R. Johnson; B.P. Howden; K.C. Carroll

doi:10.1128/JCM.01320-14

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Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates

Journal article

Open access

Peer reviewed

Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates

N.E. Holmes, J.D. Turnidge, W.J. Munckhof, J.O. Robinson, T.M. Korman, M.V.N. O'Sullivan, T.L. Anderson, S.A. Roberts, S.J.C. Warren, G.W. Coombs, …

Journal of Clinical Microbiology, Vol.52(9), pp.3384-3393

2014

DOI: https://doi.org/10.1128/JCM.01320-14

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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.

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Title: Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates
Authors/Creators: N.E. Holmes (Author/Creator) - The University of Melbourne
J.D. Turnidge (Author/Creator) - The University of Adelaide
W.J. Munckhof (Author/Creator) - The University of Queensland
J.O. Robinson (Author/Creator) - Curtin University
T.M. Korman (Author/Creator) - Monash University
M.V.N. O'Sullivan (Author/Creator) - Westmead Hospital
T.L. Anderson (Author/Creator) - Royal Hobart Hospital
S.A. Roberts (Author/Creator) - Auckland District Health Board
S.J.C. Warren (Author/Creator) - Royal Hobart Hospital
G.W. Coombs (Author/Creator) - Curtin University
H-L Tan (Author/Creator) - Curtin University
W. Gao (Author/Creator) - Austin Health
P.D.R. Johnson (Author/Creator) - The University of Melbourne
B.P. Howden (Author/Creator) - Austin Health
K.C. Carroll (Author/Creator)
Publication Details: Journal of Clinical Microbiology, Vol.52(9), pp.3384-3393
Publisher: American Society for Microbiology
Identifiers: 991005540291807891
Copyright: © 2014, American Society for Microbiology.
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.23 Antibiotics & Antimicrobials; 1.23.173 MRSA and VRE
Web Of Science research areas: Microbiology
ESI research areas: Microbiology