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

Natasha Holmes, John D Turnidge, Wendy J Munckhof, J Owen Robinson, Tony Korman, Matthew V N O'Sullivan, Tara L Anderson, Sally A Roberts, Sanchia J C Warren, Geoffrey W Coombs, Hui-Leen Tan, Wei Gao, Paul Donald Russell Johnson, Benjamin Peter Howden

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)3384 - 3393
Number of pages10
JournalJournal of Clinical Microbiology
Volume52
Issue number9
DOIs
Publication statusPublished - 2014

Cite this

Holmes, N., Turnidge, J. D., Munckhof, W. J., Robinson, J. O., Korman, T., O'Sullivan, M. V. N., ... Howden, B. P. (2014). Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates. Journal of Clinical Microbiology, 52(9), 3384 - 3393. https://doi.org/10.1128/JCM.01320-14
Holmes, Natasha ; Turnidge, John D ; Munckhof, Wendy J ; Robinson, J Owen ; Korman, Tony ; O'Sullivan, Matthew V N ; Anderson, Tara L ; Roberts, Sally A ; Warren, Sanchia J C ; Coombs, Geoffrey W ; Tan, Hui-Leen ; Gao, Wei ; Johnson, Paul Donald Russell ; Howden, Benjamin Peter. / Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates. In: Journal of Clinical Microbiology. 2014 ; Vol. 52, No. 9. pp. 3384 - 3393.
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title = "Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates",
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.",
author = "Natasha Holmes and Turnidge, {John D} and Munckhof, {Wendy J} and Robinson, {J Owen} and Tony Korman and O'Sullivan, {Matthew V N} and Anderson, {Tara L} and Roberts, {Sally A} and Warren, {Sanchia J C} and Coombs, {Geoffrey W} and Hui-Leen Tan and Wei Gao and Johnson, {Paul Donald Russell} and Howden, {Benjamin Peter}",
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Holmes, N, Turnidge, JD, Munckhof, WJ, Robinson, JO, Korman, T, O'Sullivan, MVN, Anderson, TL, Roberts, SA, Warren, SJC, Coombs, GW, Tan, H-L, Gao, W, Johnson, PDR & Howden, BP 2014, 'Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates' Journal of Clinical Microbiology, vol. 52, no. 9, pp. 3384 - 3393. https://doi.org/10.1128/JCM.01320-14

Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates. / Holmes, Natasha; Turnidge, John D; Munckhof, Wendy J; Robinson, J Owen; Korman, Tony; O'Sullivan, Matthew V N; Anderson, Tara L; Roberts, Sally A; Warren, Sanchia J C; Coombs, Geoffrey W; Tan, Hui-Leen; Gao, Wei; Johnson, Paul Donald Russell; Howden, Benjamin Peter.

In: Journal of Clinical Microbiology, Vol. 52, No. 9, 2014, p. 3384 - 3393.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates

AU - Holmes, Natasha

AU - Turnidge, John D

AU - Munckhof, Wendy J

AU - Robinson, J Owen

AU - Korman, Tony

AU - O'Sullivan, Matthew V N

AU - Anderson, Tara L

AU - Roberts, Sally A

AU - Warren, Sanchia J C

AU - Coombs, Geoffrey W

AU - Tan, Hui-Leen

AU - Gao, Wei

AU - Johnson, Paul Donald Russell

AU - Howden, Benjamin Peter

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://jcm.asm.org/content/52/9/3384.full.pdf

U2 - 10.1128/JCM.01320-14

DO - 10.1128/JCM.01320-14

M3 - Article

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SP - 3384

EP - 3393

JO - Journal of Clinical Microbiology

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SN - 0095-1137

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