A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections

Microb Drug Resist. Winter 2004;10(4):346-53. doi: 10.1089/mdr.2004.10.346.

Abstract

In recent years, the emergence of Staphylococcus aureus strains with reduced susceptibility to glycopeptides has raised considerable concern. We studied the efficacy of vancomycin and teicoplanin, as well as cloxacillin and cefotaxime, against the infection caused by four S. aureus strains with different glycopeptide and beta-lactam susceptibilities (strains A, B, C, and D; MICs for vancomycin of 1, 2, 4, and 8 microg/ml respectively), using a modified model of mouse peritonitis. This optimized model appeared to be straightforward and reproducible, and was able to detect low differences in bacterial killing between antibiotics and also between different S. aureus strains. Bactericidal activities in peritoneal fluid for vancomycin, teicoplanin, cloxacillin, and cefotaxime decreased from -2.98, -2.36, -3.22, and -3.57 log(10) cfu/ml, respectively, in infection by strain A (MICs for vancomycin and cloxacillin of 1 and 0.38 microg/ml, respectively) to -1.22, -0.65, -1.04, and +0.24 in peritonitis due to strain D (MICs for vancomycin and cloxacillin of 8 and 1,024 microg/ml). Our data confirm the superiority of beta-lactams against methicillin-susceptible S. aureus and show that bactericidal activity of glycopeptides decreases significantly with slight increases in MICs; this finding suggests a reduced efficacy of glycopeptides in the treatment of serious glycopeptide-intermediate S. aureus infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Disease Models, Animal
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination / pharmacology*
  • Glycopeptides*
  • Methicillin Resistance
  • Mice
  • Microbial Sensitivity Tests
  • Peritonitis / drug therapy*
  • Peritonitis / microbiology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics
  • beta-Lactams / pharmacokinetics
  • beta-Lactams / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Glycopeptides
  • beta-Lactams