title: Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia.
abstract: OBJECTIVE
  To evaluate microbiological properties of methicillin-resistant Staphylococcus aureus (MRSA) during prolonged vancomycin therapy.
  
  
  METHODS
  We evaluated vancomycin susceptibility and heteroresistance, accessory gene regulator (agr) function, autolysis, biofilm production and in vitro vancomycin killing in serial MRSA bloodstream isolates obtained over a 30 month period from a patient with a chronic endovascular infection.
  
  
  RESULTS
  Despite the fact that the MRSA in this patient had the same genetic background as other clinical glycopeptide intermediate-resistant S. aureus (GISA) isolates, vancomycin administered for 9 months, maintaining serum concentrations >10 mg/L, did not select for GISA. Minimal changes in vancomycin susceptibility were detected using agar dilution and population analysis methods. We noted increases in delta haemolysin production, autolysis and the bactericidal effects of vancomycin in vitro against the MRSA obtained after prolonged vancomycin suppressive therapy was discontinued.
  
  
  CONCLUSIONS
  Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.
authors.affiliation: Westchester Medical Center and New York Medical College, Valhalla, USA. george_sakoulas@nymc.edu
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: Howard S
authors.initials: HS
authors.lastname: Gold
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cohen
authors.forename: Lata
authors.initials: L
authors.lastname: Venkataraman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Moellering
authors.forename: George M
authors.initials: GM
authors.lastname: Eliopoulos
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology; D001426:Bacterial Proteins / Q000378:metabolism; D001433:Bacteriolysis; D006460:Hemolysin Proteins; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D012008:Recurrence; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D013997:Time Factors; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006460:Hemolysin Proteins; D014640:Vancomycin; C025994:delta hemolysin protein, Staphylococcus aureus