title: Adaptation of methicillin-resistant Staphylococcus aureus in the face of vancomycin therapy.
abstract: For the past 2 decades, vancomycin has served as the cornerstone of therapy against serious methicillin-resistant Staphylococcus aureus infections. This role is increasingly challenged by questions of efficacy, including reduced efficacy against infections caused by glycopeptide-intermediate S. aureus strains. In an evaluation of clinical glycopeptide-intermediate S. aureus isolates and serial, clinical methicillin-resistant S. aureus isolates obtained from patients receiving vancomycin for the treatment of bacteremia, we found that loss of function of the accessory gene regulator operon may confer a survival advantage to S. aureus under vancomycin selection pressure, particularly in strains with the accessory gene regulator group II genotype. Other advantages in a nosocomial setting may include enhancement of biofilm formation and promotion of physiologic changes supporting colonization. We conclude that loss of accessory gene regulator function in methicillin-resistant S. aureus might, in part, explain the decreased efficacy of vancomycin in the therapy of methicillin-resistant S. aureus bacteremia, thus highlighting the need to reevaluate the criteria of susceptibility to vancomycin.
authors.affiliation: Westchester Medical Center, Division of Infectious Diseases, New York Medical College, Valhalla, NY 10595, USA. george_sakoulas@nymc.edu
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Robert C
authors.initials: RC
authors.lastname: Moellering
authors.forename: George M
authors.initials: GM
authors.lastname: Eliopoulos
mesh_terms: D000220:Adaptation, Biological / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D005838:Genotype; D006801:Humans; D016106:Methicillin Resistance; D009876:Operon / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014640:Vancomycin / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D020713:Vancomycin Resistance / Q000187:drug effects / Q000235:genetics
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015534:Trans-Activators; D014640:Vancomycin