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Vancomycin-intermediate Staphylococcus aureus selected during vancomycin therapy of experimental endocarditis are not detected by culture-based diagnostic procedures and persist after treatment arrest

Moreillon, Philippe ; Bizzini, Alain ; Giddey, Marlyse ; Vouillamoz, Jacques ; Entenza, José M.

In: Journal of Antimicrobial Chemotherapy, 2012, vol. 67, no. 3, p. 652-660

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    Titre
    • Vancomycin-intermediate Staphylococcus aureus selected during vancomycin therapy of experimental endocarditis are not detected by culture-based diagnostic procedures and persist after treatment arrest
    Auteur
    • Moreillon, Philippe. Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    • Bizzini, Alain. Institute of Microbiology, University of Lausanne and University Hospital Center, Lausanne, Switzerland
    • Giddey, Marlyse. Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    • Vouillamoz, Jacques. Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    • Entenza, José M.. Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of Antimicrobial Chemotherapy, 2012, vol. 67, no. 3, p. 652-660. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:296906
    Summary
    Objectives Laboratory detection of vancomycin-intermediate Staphylococcus aureus (VISA) and their heterogeneous VISA (hVISA) precursors is difficult. Thus, it is possible that vancomycin failures against supposedly vancomycin-susceptible S. aureus are due to undiagnosed VISA or hVISA. We tested this hypothesis in experimental endocarditis. Methods Rats with aortic valve infection due to the vancomycin-susceptible (MIC 2 mg/L), methicillin-resistant S. aureus M1V2 were treated for 2 days with doses of vancomycin that mimicked the pharmacokinetics seen in humans following intravenous administration of 1 g of the drug every 12 h. Half of the treated animals were killed 8 h after treatment arrest and half 3 days thereafter. Population analyses were done directly on vegetation homogenates or after one subculture in drug-free medium to mimic standard diagnostic procedures. Results Vancomycin cured 14 of 26 animals (54%; P < 0.05 versus controls) after 2 days of treatment. When vegetation homogenates were plated directly on vancomycin-containing plates, 6 of 13 rats killed 8 h after treatment arrest had positive cultures, 1 of which harboured hVISA. Likewise, 6 of 13 rats killed 3 days thereafter had positive valve cultures, 5 of which harboured hVISA. However, one subculture of vegetations in drug-free broth was enough to revert all the hVISA phenotypes to the susceptible pattern of the parent. Thus, vancomycin selected for hVISA during therapy of experimental endocarditis due to vancomycin-susceptible S. aureus. These hVISA were associated with vancomycin failure. The hVISA phenotype persisted in vivo, even after vancomycin arrest, but was missed in vitro after a single passage of the vegetation homogenate on drug-free medium. Conclusions hVISA might escape detection in clinical samples if they are subcultured before susceptibility tests