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. 2009 Nov 1;200(9):1355-66.
doi: 10.1086/606027.

Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance

In-Gyu Bae  1 , Jerome J Federspiel, José M Miró, Christopher W Woods, Lawrence Park, Michael J Rybak, Thomas H Rude, Suzanne Bradley, Suzana Bukovski, Cristina Garcia de la Maria, Souha S Kanj, Tony M Korman, Francesc Marco, David R Murdoch, Patrick Plesiat, Marta Rodriguez-Creixems, Porl Reinbott, Lisa Steed, Pierre Tattevin, Marie-Françoise Tripodi, Karly L Newton, G Ralph Corey, Vance G Fowler Jr; International Collaboration on Endocarditis-Microbiology Investigator
Collaborators, Affiliations

Heterogeneous vancomycin-intermediate susceptibility phenotype in bloodstream methicillin-resistant Staphylococcus aureus isolates from an international cohort of patients with infective endocarditis: prevalence, genotype, and clinical significance

In-Gyu Bae et al. J Infect Dis. .

Abstract

Background: The significance of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) is unknown. Using a multinational collection of isolates from methicillin-resistant S. aureus (MRSA) infective endocarditis (IE), we characterized patients with IE with and without hVISA, and we genotyped the infecting strains.

Methods: MRSA bloodstream isolates from 65 patients with definite IE from 8 countries underwent polymerase chain reaction (PCR) for 31 virulence genes, pulsed-field gel electrophoresis, and multilocus sequence typing. hVISA was defined using population analysis profiling.

Results: Nineteen (29.2%) of 65 MRSA IE isolates exhibited the hVISA phenotype by population analysis profiling. Isolates from Oceania and Europe were more likely to exhibit the hVISA phenotype than isolates from the United States (77.8% and 35.0% vs 13.9%; P < .001). The prevalence of hVISA was higher among isolates with a vancomycin minimum inhibitory concentration of 2 mg/L (P = .026). hVISA-infected patients were more likely to have persistent bacteremia (68.4% vs 37.0%; P = .029) and heart failure (47.4% vs 19.6%; P = .033). Mortality did not differ between hVISA- and non-hVISA-infected patients (42.1% vs 34.8%, P = .586). hVISA and non-hVISA isolates were genotypically similar.

Conclusions: In these analyses, the hVISA phenotype occurred in more than one-quarter of MRSA IE isolates, was associated with certain IE complications, and varied in frequency by geographic region.

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Conflict of interest statement

Dr. Bae, Rude, Newton, Park, Dr. Marco and Dr. Garcia-de-la-Maria did not have any conflict of interest.

Potential Conflict of Interest: Dr. Fowler has served as a consultant for Astellas, Cubist, Inhibitex, Merck, Johnson & Johnson, Leo Pharmaceuticals; reports having received grant or research support from Astellas, Cubist, Merck, Theravance, Inhibitex, Cerexa, National Institute of Health; reports having received honoraria from Arpida, Astellas, Cubist, Inhibitex, Merck, Pfizer, Targanta, Theravance, Ortho-McNeil; has served as a membership on advisory committee for Cubist; has served as a speaker’s bureau for Cubist. Dr. Corey serves as a consultant for (money for these meetings is donated to the Global Health Fund at Duke University) Theravance, Cubist, AstraZeneca Astellas, Cerexa, Merck, Cempra, Pfizer, Arpida, GSK, Inimex, Targanta, and Trius; receives research contracts/grant (these relationships result in funds being provided through Duke University to support research or salary) from Theravance, Innocoll, Cerexa, Cempra. Dr. Kanj is on the advisory board for Sanofi Aventis. Pharm.D. Rybak is a speaker for Cubist, Wyeth, Pfizer, Astellas, Theravance Forest, Ortho-McNeil, and Targanta. Dr. Woods has served as a consultant for Roche Molecular; reports having received grant or research support from Cubist, Roche Molecular; has served as a membership on advisory committee for BioMerieux, Astellas; involved clinical trial of BioMerieux and Cepheid.

Figures

Figure 1
Figure 1
Prevalence by geographic region of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) phenotype among MRSA bloodstream isolates from patients with infective endocarditis. Percentages of patients with hVISA phenotype are specified above each column.
Figure 2
Figure 2
Dendrogram of pulsed-field gel electrophoresis profiles of 65 MRSA bloodstream isolates from patients with infective endocarditis. The clonal complex/sequence type, geographic region of origin, and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) status of each isolate is also represented. CC = clonal complex; ST = sequence type as defined by multilocus sequence typing; Region = Geographic region of source patient; Group = vancomycin-susceptible S. aureus (VSSA) and hVISA.
See this image and copyright information in PMC

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