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A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections
Alejandro Domenech1, Sandra Ribes, Carmen Cabellos
1Laboratory of Experimental Infection, Infectious Diseases Service, Hospital Universitari de Bellvitge, Barcelona, Spain. adomenech@bell.ub.es
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.
Insights
Emerging Staphylococcus aureus strains resistant to glycopeptides are a concern. Beta-lactams are superior to glycopeptides against these strains, as their efficacy decreases with rising minimum inhibitory concentrations (MICs).
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Rising concern over Staphylococcus aureus strains with reduced glycopeptide susceptibility.
- Need to evaluate antibiotic efficacy against strains with varying resistance profiles.
Purpose of the Study:
- To assess the efficacy of vancomycin, teicoplanin, cloxacillin, and cefotaxime against Staphylococcus aureus strains with differing glycopeptide and beta-lactam susceptibilities.
- To validate a modified mouse peritonitis model for detecting subtle differences in antibiotic activity.
Main Methods:
- Utilized a modified mouse peritonitis model to test four Staphylococcus aureus strains (A, B, C, D) with varying vancomycin MICs (1-8 microg/ml).
- Measured bactericidal activities of vancomycin, teicoplanin, cloxacillin, and cefotaxime in peritoneal fluid.
- Determined minimum inhibitory concentrations (MICs) for vancomycin and cloxacillin for each strain.
Main Results:
- Bactericidal activity of all tested antibiotics decreased as vancomycin MICs increased from strain A to strain D.
- Vancomycin and teicoplanin efficacy significantly reduced with increasing MICs, particularly for strain D (vancomycin MIC 8 microg/ml).
- Beta-lactams (cloxacillin, cefotaxime) demonstrated superior bactericidal activity compared to glycopeptides against susceptible strains.
Conclusions:
- Beta-lactam antibiotics are more effective than glycopeptides against methicillin-susceptible Staphylococcus aureus.
- Reduced susceptibility to glycopeptides in Staphylococcus aureus correlates with decreased in vivo bactericidal activity.
- Glycopeptides may have reduced efficacy in treating serious infections caused by glycopeptide-intermediate Staphylococcus aureus.
