Pharmacotherapeutic group: Antibacterial for systemic use, first-generation cephalosporin. ATCvet code: QJ01DB01
Pharmacodynamic properties
Cefalexin monohydrate is a bactericidal antibiotic of the cephalosporin family, obtained by hemi-synthesis of the 7-amino cephalosporanic nucleus.
Cefalexin acts by inhibiting the nucleopeptide synthesis of the bacterial wall. Cephalosporins interfere with transpeptidation by acylating the enzyme making it unable to cross-link muramic acid-containing peptidoglycan strands. The inhibition of the biosynthesis of the material required to build the cell wall results in a defective cell wall and consequently osmotically unstable to protoplasts. The combined action results in cell lysis and filament formation. Cefalexin is active against Gram positive and Gram negative bacteria such as Staphylococcus spp. (including penicillin-resistant strains), Streptococcus spp.,and Escherichia coli. Cefalexin is not inactivated by β-lactamases produced by Gram positive bacteria. However, beta-lactamases produced by Gram-negative bacteria can inhibit cefalexin by hydrolysis of the beta-lactam cycle.
Resistance to cefalexin may be due to one of the following mechanisms of resistance. Firstly, the production of various beta-lactamases (cephalosporinase), that inactivate the antibiotic, is the most prevalent mechanism among Gram-negative bacteria. Secondly, a decreased affinity of the PBPs (penicillin-binding proteins) for beta-lactam drugs is frequently involved for beta-lactam resistant Gram-positive bacteria. Lastly, efflux pumps, extruding the antibiotic from the bacterial cell, and structural changes in porins, reducing passive diffusion of the drug through the cell wall, may contribute to improve the resistant phenotype of a bacterium.
Well-known cross-resistance (involving the same resistance mechanism) exists between antibiotics belonging to the beta-lactam group due to structural similarities. It occurs with β-lactamase enzymes, structural changes in porins or variations in efflux pumps. Co-resistance (different resistance mechanisms involved) has been described in E.coli due to a plasmid harbouring various resistance genes.
MICs parameters available for Staphylococcus spp. and Pasteurella multocida are:
Staphylococcus spp MIC 50 2 µg/ml MIC90 2 µg/ml
Pasteurella multocida MIC 50 2 µg/ml MIC90 4 µg/ml
Pharmacokinetic properties
In cats, the bioavailability after oral administration is around 56%.
In cats, after a single oral administration of 18.5 mg/kg of cefalexin, the plasmatic peak was reached after 1.6 h with a concentration of 22 µg/ml.
Cefalexin was detected in plasma till 24 hours after administration.
The diffusion of cefalexin in tissue is high. Cefalexin is mainly eliminated by urinary route (85%) under active form, urinary concentration peaks are significantly higher than plasmatic concentration peaks.