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Relevance of protein binding to cephalosporin antimicrobial activity in vivo
B Mays1, L Short, M J Hershman
1Department of Surgery, University of Louisville, Ky.
Abstract:
Protein binding, serum kinetics and minimum inhibitory concentrations (MICs) for Staphylococcus aureus were determined for cefoxitin, cefazolin, ceftazidime and ceftriaxone in the rabbit. MICs of cefazolin and cefoxitin were also measured for Escherichia coli. Varying concentrations of the bacteria were administered intradermally to create areas of cellulitis, which were quantified as mean erythematous areas (EAs). Despite large differences in protein binding of the antibiotics (range 12-88%) and antibiotic dosing to allow serum concentrations to drop below the respective MICs, there was no statistical difference in the mean EAs of the animals after bacterial challenge. Antibiotic protein binding did not alter the course of cellulitis nor correlate with bacterial MIC in this model.
Insights
Antibiotic protein binding did not impact Staphylococcus aureus or Escherichia coli cellulitis treatment in rabbits. Despite varying protein binding and serum concentrations, no significant difference in erythematous areas was observed.
Area of Science:
- Pharmacology
- Infectious Diseases
- Dermatology
Background:
- Antibiotic efficacy is influenced by factors like protein binding and serum kinetics.
- Understanding these factors is crucial for effective treatment of bacterial infections, such as cellulitis.
Purpose of the Study:
- To evaluate the impact of protein binding and serum kinetics of four antibiotics on Staphylococcus aureus and Escherichia coli-induced cellulitis in a rabbit model.
- To determine if antibiotic protein binding correlates with minimum inhibitory concentrations (MICs) and affects treatment outcomes.
Main Methods:
- Determined protein binding, serum kinetics, and MICs for cefoxitin, cefazolin, ceftazidime, and ceftriaxone in rabbits.
- Induced intradermal cellulitis in rabbits using varying concentrations of Staphylococcus aureus and Escherichia coli.
- Quantified cellulitis severity by measuring mean erythematous areas (EAs).
Main Results:
- Significant variations in antibiotic protein binding (12-88%) and serum concentrations below MICs were observed.
- No statistical difference in mean EAs was found between antibiotic treatment groups.
- Antibiotic protein binding did not influence the course of cellulitis or correlate with bacterial MICs in this model.
Conclusions:
- Antibiotic protein binding and serum kinetics did not significantly affect the treatment of experimental Staphylococcus aureus and Escherichia coli cellulitis in rabbits.
- The studied antibiotics demonstrated comparable efficacy in resolving experimental cellulitis, irrespective of their protein binding levels.