Pharmacotherapeutic group: anti-infective for systemic use; amoxicillin and enzyme inhibitor.
ATCvet code: QJ01CR02
Pharmacodynamic properties
Amoxicillin is an aminobenzylpenicillin from the β-lactam penicillin family which prevents the bacterial cell wall formation by interfering with the final step of peptidoglycan synthesis.
Clavulanic acid is an irreversible inhibitor of intracellular and extracellular β-lactamases which protects amoxicillin from inactivation by many β-lactamases.
Amoxicillin/clavulanate has a wide range of activity which includes β-lactamase producing strains of both Gram-positive and Gram-negative aerobes, facultative anaerobes and obligate anaerobes.
According to CLSI document VET01-S2, amoxicillin/clavulanic acid breakpoints are for feline skin and soft tissue infections and for the following organisms (Staphylococcus spp.,
Streptococcus spp., Escherichia coli and Pasteurella multocida): sensitive: MIC <0.25/0.12 μg/ml, resistant: MIC > 1/0.5 μg/ml.
In absence of specific veterinary breakpoints, the following human derived breakpoints (M100-S document) could be used for any other animal species/bacterial species/infection type combination:
Staphylococci: sensitive: MIC < 4/2 μg/ml, resistant: MIC > 8/4 μg/ml
Other organisms: sensitive: MIC < 8/4 μg/ml, resistant: MIC > 32/16 μg/ml
In dog periodontal infections in Europe (isolates of the year 2002 from France, Germany and Belgium) amoxicillin/clavulanic acid combination in a ratio 2/1 showed the following data on sensitivity:
Pasteurellaceae: MIC90: 0.4/0.2 μg/ml,
Streptococcus spp.: MIC90: 0.4/0.2 μg/ml,
Escherichia coli: MIC90: 5.3/2.6 μg/ml,
In cat and dog dermatological infections in Europe (isolates between the year 2010 and 2013 from The Netherlands, France, Germany, The United Kingdom and Belgium) amoxicillin/clavulanic acid combination in a ratio 2/1 showed the following data on sensitivity:
Data for the period 2010-2013 | n | Range of MIC (μg/mL) | MIC50 (μg/mL) | MIC90 (μg/mL) |
Pasteurella multocida | 4-17 | 0.06/0.03 - 0.5/0.25 | 0.166/0.0832 | 0.232/0.1162 |
Staphylococcus spp | 29-33 | 0.06/0.03 - 32/16 | 0.102/0.051 - 0.170/0.085 - | 0.835/0.418 - 11.578/5.789 |
Streptococcus spp1 | 11-12 | 0.015/0.0080. 0.03/0.015 | 0.013/0.006 - 0.027/0.014 | 0.023/0.012 - 0.027/0.014 |
Escherichia coli | 1-4 | 1/0.5 - 64/32 | ND | ND |
1 MIC values determined in 2012 and 2013;
2 MIC50 and MIC90 could be determined in 2013 only;
ND: Not Determined due to low sample size
Resistance to β-lactam antibiotics is mainly mediated by β-lactamases which hydrolyze antibiotics such as amoxicillin.
Susceptibility and resistance patterns can vary with geographical area and bacterial strain, and may change over time.
Pharmacokinetic particulars
After oral administration at the recommended dose in dogs and cats, the absorption of amoxicillin and clavulanic acid is fast. In dogs, the maximum plasma concentration of amoxicillin of 8.5 μg/ml is reached in 1.4 hours and the maximum plasma concentration of clavulanic acid of 0.9 μg/ml is reached in 0.9 hours. Half-life is 1 hour in dogs for both substances.
In cats, the maximum plasma concentration of amoxicillin of 6.6 μg/ml is reached in 1.8 hours and the maximum plasma concentration of clavulanic acid of 3.7 μg/ml is reached in 0.75 hours. Half-life is 1 to 2 hours in cats for both substances.
Elimination is also fast. 12 % of the amoxicillin and 17 % of clavulanic acid is excreted in the urine. The remainder is excreted as inactive metabolites.
After repeated oral administration of the recommended dose in dogs and cats, there is no accumulation of amoxicillin or clavulanic acid and the steady state is reached rapidly after first administration.