ATCvet code: QJ01CR02
Pharmacodynamics
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. The antimicrobial spectrum relevant for dog’s and cat’s indications is summarized in the two tables below.
Summary of susceptibility for dog target bacteria:
Target bacteria in each indication | n | Range of MIC (µg/mL) | MIC50 (µg/mL) | MIC90 (µg/mL) | Clinical breakpoints (I/R) |
Skin and soft tissues | | | | |
Staphylococcus spp | 431* | 0.03-32 | 0.12 | 1 | 0.25/1 |
S. aureus | 38* | 0.12-16 | 0.5 | 2 | 0.25/1 |
S. intermedius group | 343* | 0.03-8 | 0.12 | 0.5 | 0.25/1 |
Coagulase-negative | 49* | 0.03-32 | 0.12 | 2 | 0.25/1 |
Staphylococcus spp | | | | | |
Streptococcus spp | 142* | 0.015-0.06 | ≤0.015 | ≤0.015 | – |
Streptococcus canis | 127* | 0.015-0.06 | ≤0.015 | ≤0.015 | – |
Streptococcus dysgalactiae | 12* | 0.015 | ≤0.015 | ≤0.015 | – |
Pasteurella spp | 22* | 0.03-0.25 | 0.12 | 0.25 | – |
Respiratory | |
Staphylococcus spp | 112* | 0.06-8 | 0.12 | 0.5 | – |
S. intermedius group | 90* | 0.06-8 | 0.12 | 0.25 | – |
S. aureus | 22* | 0.12-8 | 0.25 | 1 | – |
|
Dental | | | | | |
Streptococcus spp | 16** | 0.008 - 1 | 0.014 | 0.4 | – |
Pasteurella spp | 68** | 0.03 - 64 | 0.124 | 0.4 | – |
Urinary |
Escherichia coli | 236* | 1-32 | 4 | 16 | 8/- |
Klebsiella spp | 33* | 0.5-32 | 2 | 32 | 8/- |
Proteus spp | 66* | 0.5-16 | 1 | 8 | 8/- |
Digestive |
Escherichia coli | - * | 1-32 | 4 | 8 | – |
Clavaseptin: Dog |
Table | | | | | |
Breakpoints are from CLSI VET01-S7.
* MIC values determined from bacteria collected in Europe in 2021-2022 (ComPath-IV survey). Susceptibility of digestive isolates is assumed similar to that of the same bacteria in other types of infection.
** MIC values determined from bacteria collected from dog dental infections in Europe in 2002.
- Missing information.
The two main mechanisms of resistance to amoxicillin/clavulanic acid are inactivation by β- lactamases that are not inhibited by clavulanic acid, and alteration of penicillin binding proteins, which lead to co-resistance to other β-lactam antibiotics. Impermeability of bacteria or efflux pump mechanisms may also contribute to bacterial resistance, including co- and cross-resistance. Susceptibility and resistance patterns can vary with geographical area and bacterial strain, and may change over time.
Pseudomonas spp are naturally resistant to the amoxicillin – clavulanic acid combination. Methicillin resistant S. aureus (MRSA) and methicillin resistant S. pseudintermedius (MRSP) isolates have been identified in cats and dogs and should be considered resistant to all β-lactam including amoxicillin/clavulanic acid combination.
High resistances (up to 100%) have been reported in E. coli isolates from skin and soft tissue infections in dogs.
Pharmacokinetic particulars
After oral administration at the recommended dose in dogs, the absorption of amoxicillin and clavulanic acid is fast. 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.
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, there is no accumulation of amoxicillin or clavulanic acid and the steady state is reached rapidly after first administration.