title: Vancomycin-intermediate Staphylococcus aureus selected during vancomycin therapy of experimental endocarditis are not detected by culture-based diagnostic procedures and persist after treatment arrest.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Fundamental Microbiology,  University of Lausanne, Lausanne,  Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreillon
authors.forename: Alain
authors.initials: A
authors.lastname: Bizzini
authors.forename: Marlyse
authors.initials: M
authors.lastname: Giddey
authors.forename: Jacques
authors.initials: J
authors.lastname: Vouillamoz
authors.forename: José M
authors.initials: JM
authors.lastname: Entenza
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001431:Bacteriological Techniques / Q000379:methods*; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D007275:Injections, Intravenous; D051381:Rats; D012641:Selection, Genetic; D012680:Sensitivity and Specificity; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D014640:Vancomycin / Q000008:administration & dosage*; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin