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Combinatorial phenotypic signatures distinguish persistent from resolving methicillin-resistant Staphylococcus aureus bacteremia isolates.

Publication ,  Journal Article
Seidl, K; Bayer, AS; Fowler, VG; McKinnell, JA; Abdel Hady, W; Sakoulas, G; Yeaman, MR; Xiong, YQ
Published in: Antimicrob Agents Chemother
February 2011

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) (positive blood cultures after ≥7 days of therapy) represents a clinically challenging subset of invasive MRSA infections. In this investigation, we examined the potential correlation of specific virulence signatures with PB versus resolving MRSA bacteremia (RB) (negative blood cultures within 2 to 4 days of therapy) strains. Thirty-six MRSA isolates from patients enrolled in a recent multinational clinical trial were studied for (i) susceptibility to host defense cationic peptides (HDPs) (i.e., thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide 1 [hNP-1]); (ii) adherence to host endovascular ligands (fibronectin) and cells (endothelial cells); and (iii) biofilm formation. We found that PB isolates exhibited significantly reduced susceptibilities to tPMPs and hNP-1 (P < 0.001 and P = 0.023, respectively). There was no significant association between the PB outcome and fibronectin binding, endothelial cell binding, or biofilm formation (P = 0.25, 0.97, and 0.064 versus RB strains, respectively). However, multiple logistic regression analysis revealed that the PB outcome was significantly associated with the combination of reduced susceptibilities to HDPs and extent of biofilm formation (P < 0.0001). Similar results were obtained in a second analysis using days of bacteremia as a continuous outcome, showing that reduced HDP susceptibilities and increased biofilm formation cocontributed to predict the duration of bacteremia. Our data indicate that PB isolates have specific pathogenic signatures independent of conventional antimicrobial susceptibility. These combinatorial mosaics can be defined and used to prospectively distinguish PB from RB strains in advance and potentially to predict ultimate clinical outcomes.

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

February 2011

Volume

55

Issue

2

Start / End Page

575 / 582

Location

United States

Related Subject Headings

  • beta-Thromboglobulin
  • alpha-Defensins
  • Virulence
  • Staphylococcal Infections
  • Phenotype
  • Microbiology
  • Microbial Sensitivity Tests
  • Methicillin-Resistant Staphylococcus aureus
  • Humans
  • Fibronectins
 

Citation

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Seidl, K., Bayer, A. S., Fowler, V. G., McKinnell, J. A., Abdel Hady, W., Sakoulas, G., … Xiong, Y. Q. (2011). Combinatorial phenotypic signatures distinguish persistent from resolving methicillin-resistant Staphylococcus aureus bacteremia isolates. Antimicrob Agents Chemother, 55(2), 575–582. https://doi.org/10.1128/AAC.01028-10
Seidl, Kati, Arnold S. Bayer, Vance G. Fowler, James A. McKinnell, Wessam Abdel Hady, George Sakoulas, Michael R. Yeaman, and Yan Q. Xiong. “Combinatorial phenotypic signatures distinguish persistent from resolving methicillin-resistant Staphylococcus aureus bacteremia isolates.Antimicrob Agents Chemother 55, no. 2 (February 2011): 575–82. https://doi.org/10.1128/AAC.01028-10.
Seidl K, Bayer AS, Fowler VG, McKinnell JA, Abdel Hady W, Sakoulas G, et al. Combinatorial phenotypic signatures distinguish persistent from resolving methicillin-resistant Staphylococcus aureus bacteremia isolates. Antimicrob Agents Chemother. 2011 Feb;55(2):575–82.
Seidl, Kati, et al. “Combinatorial phenotypic signatures distinguish persistent from resolving methicillin-resistant Staphylococcus aureus bacteremia isolates.Antimicrob Agents Chemother, vol. 55, no. 2, Feb. 2011, pp. 575–82. Pubmed, doi:10.1128/AAC.01028-10.
Seidl K, Bayer AS, Fowler VG, McKinnell JA, Abdel Hady W, Sakoulas G, Yeaman MR, Xiong YQ. Combinatorial phenotypic signatures distinguish persistent from resolving methicillin-resistant Staphylococcus aureus bacteremia isolates. Antimicrob Agents Chemother. 2011 Feb;55(2):575–582.

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

February 2011

Volume

55

Issue

2

Start / End Page

575 / 582

Location

United States

Related Subject Headings

  • beta-Thromboglobulin
  • alpha-Defensins
  • Virulence
  • Staphylococcal Infections
  • Phenotype
  • Microbiology
  • Microbial Sensitivity Tests
  • Methicillin-Resistant Staphylococcus aureus
  • Humans
  • Fibronectins