Cefalexin monohydrate, the active ingredient of the Therios tablets, 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 pathogens such as Streptococcus spp. and Staphylococcus spp. (including penicillin-resistant strains) and Gram negative pathogens such as Proteus mirabilis and some strains of Escherichia coli and Klebsiella spp.

Cefalexin is active against Methicillin-susceptible staphylococci including penicillin-resistant strains not against Methicillin-resistant staphylococci.

Cefalexin is active against most beta-lactamase-producing Gram positive bacteria and has moderate activity against certain non-transferable (chromosomal) beta-lactamase-producing Gram negative Enterobacteriaceae and fastidious Gram negatives.

Resistance is plasmid-mediated or transmitted by chromosomal route.

Cefalexin has a time-dependent bactericidal activity against Staphylococcus spp. and Pasteurella multocida.

CLSI cefalexin veterinary breakpoints are available for dogs in Staphylococcus aureus, Staphylococcus pseudintermedius, Streptococci-β-hemolytic group and Escherichia coli in skin and soft tissue infections. (CLSI, July 2013).

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.

After single oral administration of the recommended dosage of 15 mg cefalexin per kg bodyweight to Beagle dogs, plasma concentrations were observed within 30 minutes. The plasma peak was observed at 1.33 h with a plasma concentration of 21.2 μg/ml. The bioavailability of the active was over 90%. Cefalexin was detected until 24 hours after the administration. The first urine specimen was collected within 2 to 12 hours with peak concentrations of cefalexin measured at 430 to 2758 μg/ml within 12 hours.

After repeated oral administration of the same dosage, twice a day for 7 days, plasma peaks occurred 2 hours later with a concentration of 20 μg/ml. Over the treatment period concentrations were maintained above 1 μg/ml. The mean elimination half life is 2 hours. Skin levels were around 5.8 to 6.6 μg/g 2 hours after treatment.