Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia

J Antimicrob Chemother. 2006 Apr;57(4):699-704. doi: 10.1093/jac/dkl030. Epub 2006 Feb 7.

Abstract

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacteremia / drug therapy
  • Bacteremia / microbiology
  • Bacterial Proteins / metabolism
  • Bacteriolysis
  • Hemolysin Proteins
  • Humans
  • Methicillin Resistance*
  • Microbial Sensitivity Tests
  • Recurrence
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / classification
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / isolation & purification
  • Time Factors
  • Treatment Outcome
  • Vancomycin / administration & dosage*
  • Vancomycin / pharmacology
  • Vancomycin / therapeutic use
  • Vancomycin Resistance*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Hemolysin Proteins
  • Vancomycin
  • delta hemolysin protein, Staphylococcus aureus