Phenotypic and genotypic characteristics of persistent methicillin-resistant Staphylococcus aureus bacteremia in vitro and in an experimental endocarditis model.
BACKGROUND
Persistent MRSA bacteremia (PB) represents an important subset of Staphylococcus aureus infections and correlates with poor clinical outcomes.


METHODS
We profiled relevant in vitro phenotypic and genotypic characteristics of MRSA isolates from 39 persons with bacteremia (21 had PB and 18 had resolving bacteremia [RB]). We also compared the intrinsic virulence and responsiveness to vancomycin of selected PB and RB strains in an experimental endocarditis model (IE).


RESULTS
PB and RB isolates differed significantly with regard to several in vitro characteristics that are believed to impact endovascular infections. PB isolates exhibited significantly more resistance to the cationic defensin hNP-1, enhanced membrane fluidity, and substantially greater adhesion to fibronectin, fibrinogen, and endothelial cells. Genotypically, PB isolates had higher frequency of SCCmec II, CC30, and spa 16; and higher rates of agr type III, cap8, tst-1, and cna carriage. Finally, a prototypic PB strain was more resistant to vancomycin treatment in the infective endocarditis model than a RB comparator strain, despite equivalent virulence profiles.


CONCLUSIONS
Our findings indicate that PB isolates may have specific virulence signatures that distinguish them from RB isolates. These data suggest that methods might be developed to identify patients at higher risk for PB in real-time, thereby optimizing the effectiveness of anti-MRSA therapeutic strategies.
Xiong
Yan Q
YQ
Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA 90502, USA. yxiong@ucla.edu
Fowler
Vance G
VG
Yeaman
Michael R
MR
Perdreau-Remington
Francoise
F
Kreiswirth
Barry N
BN
Bayer
Arnold S
AS
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy / Q000382:microbiology*; D005838:Genotype; D006801:Humans; D016106:Methicillin Resistance; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification* / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D010641:Phenotype; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D014640:Vancomycin