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Clinical pharmacology of cefixime in unweaned calves
1Ministry of Agriculture, Kimron Veterinary Institute, Bet-Dagan, Israel.
Abstract:
Cefixime is a unique third-generation oral cephalosporin. Its in vitro activity and pharmacokinetic properties have been studied to assess its potential for use in the therapy of newborn calf infections due to gram-negative bacteria. The minimum inhibitory concentrations of cefixime for 90% (MIC90) of field isolates of Escherichia coli, Salmonella and Pasteurella were 0.10-0.40 micrograms/mL. The serum disposition kinetics of cefixime following intravenous and oral administration was evaluated. The elimination half-life of cefixime after intravenous and oral administration was 3.5-4.0 h, the steady-state volume of distribution was 0.34 L/kg and approximately 90% of the drug was bound to serum proteins. Oral absorption was comparatively slow and bioavailability values for single 5 mg/kg doses were 20.2% after the administration of 200 mg of cefixime in capsules, 28.3% after dosing an aqueous solution of cefixime and 35.7% after fasted calves received the solution of cefixime. Mean serum drug concentrations 12 h after the cefixime solution was administered orally (5 mg/kg) were 1.05 micrograms/mL for the milk-fed calves and 1.76 micrograms/mL for the fasted calves. Computations showed that mean free drug concentrations equal to the MIC50 of the drug for gram-negative pathogens associated with newborn calf infections can be maintained in tissues by multiple treatments at 5 mg/kg every 12 h or 10 mg/kg every 24 h.
Insights
Cefixime demonstrates potent in vitro activity against key gram-negative bacteria in calves. Pharmacokinetic studies suggest effective dosing regimens for treating newborn calf infections with this cephalosporin antibiotic.
Area of Science:
- Veterinary Pharmacology
- Antimicrobial Chemotherapy
Background:
- Newborn calf infections caused by gram-negative bacteria pose a significant challenge in animal health.
- Third-generation cephalosporins offer broad-spectrum activity, but their efficacy in neonates requires specific evaluation.
Purpose of the Study:
- To evaluate the in vitro antimicrobial activity of cefixime against common gram-negative pathogens in calves.
- To determine the pharmacokinetic profile of cefixime in newborn calves following intravenous and oral administration.
- To establish optimal cefixime dosing strategies for treating neonatal calf infections.
Main Methods:
- In vitro susceptibility testing of cefixime against field isolates of Escherichia coli, Salmonella, and Pasteurella.
- Intravenous and oral administration of cefixime to newborn calves to assess serum pharmacokinetics, including elimination half-life and protein binding.
- Bioavailability studies comparing different oral formulations (capsules, aqueous solution) and feeding states (milk-fed vs. fasted).
Main Results:
- Cefixime exhibited low minimum inhibitory concentrations (MIC90) against E. coli, Salmonella, and Pasteurella isolates (0.10-0.40 µg/mL).
- The elimination half-life was 3.5-4.0 hours, with approximately 90% protein binding and a steady-state volume of distribution of 0.34 L/kg.
- Oral bioavailability varied by formulation and feeding status, with fasted calves showing higher absorption (up to 35.7%) compared to milk-fed calves.
Conclusions:
- Cefixime possesses significant in vitro efficacy against major gram-negative bacterial pathogens implicated in calf infections.
- Pharmacokinetic data support the potential therapeutic use of cefixime in newborn calves.
- Calculated dosing regimens (5 mg/kg every 12 h or 10 mg/kg every 24 h) are predicted to maintain effective drug concentrations for treating these infections.