Pharmacotherapeutic group: Antibacterials for intramammary use – antibacterials and corticosteroids
ATC Vet Code: QJ51RV01
Pharmacodynamic properties:
Amoxicillin is a broad spectrum bactericidal β-lactam antibiotic. Clavulanic acid inactivates β-lactamases. This combination is effective against β-lactamase producing organisms.
Prednisolone is an anti-inflammatory corticosteroid.
In vitro, clavulanic acid and amoxicillin in combination are active against a wide range of clinically important bacteria including the following organisms which are commonly associated with bovine mastitis:
Staphylococci (including β-lactamase producing strains)
Streptococci (including S. agalactiae, S. dysgalactiae and S. uberis)
Escherichia coli (including β-lactamase producing strains)
The Minimum Inhibitory Concentrations (MICs) of these target organisms determined from samples collected in nine EU countries (namely Belgium, Czech Republic, Denmark, France, Germany, Italy, Netherlands, Spain, and the UK)1, show susceptibility to amoxicillin and clavulanic acid used in combination in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines2 on breakpoints (Table 1 and 2).
Table 1: Minimum Inhibitory Concentrations (mg/L) of Amoxicillin/Clavulanic Acid against strains from mastitis in dairy cattle in nine EU countries
| E. coli | S. aureus | CNS | S. uberis | S. dysgalactiae |
Amoxicillin/Clavulanic Acid | 8 | 1 | 0.5 | 0.5 | ≤0.03 |
Table 2: Clinical Laboratory Standards Institute (CLSI) resistance breakpoints (mg/L) for target bacteria
| E. coli | S. aureus | CNS3 | S. uberis | S. agalactiae | S. dysgalactiae |
Amoxicillin/Clavulanic Acid | ≥32 | ≥8 | ≥8 | ≥32 | ≥8 | ≥32 |
1Antimicrobial susceptibility of mastitis pathogens isolated from diseased dairy cows across Europe: VetPath monitoring results, European society of clinical microbiology and infectious diseases (ECCMID), 2015.
2Clinical and Laboratory Standards Institute (2013). Approved standards- fourth edition, CLSI document VETO01-A4, Wayne, PA, USA.
3CNS – Coagulase Negative Staphylococci
The mechanisms underlying antimicrobial resistance in Streptococcus can be acquired through the mutation of intrinsic genes or horizontal exchange of genetic material encoding resistance determinants. Mastitic strains of E. coli and Staphylococcus, are known to acquire resistance through horizontal gene transfer and bacteriophages/plasmid transfer, and also through their ability to form a biofilm.
Acquired resistance prevalence in particular to be high in E. coli. In some strains of Staphylococcus aureus (methicillin-resistant S. aureus, MRSA), and of Staphylococcus pseudintermedius, resistance to all β-lactams is conferred by the alteration of the cell wall target proteins (penicillin-binding proteins). This is often associated with resistance to multiple other antimicrobial compounds with cross resistance.
Mastitic strains of E. coli and Staphylococcus are known to acquire resistance through horizontal gene transfer and bacteriophages/plasmid transfer, and also through their own ability to form a biofilm.
Pharmacokinetic particulars
It has been documented that the pharmacokinetic characteristics of penicillins (including amoxicillin) after intramammary administration indicate rapid elimination of the drug from milk. The mean residence time has a several-fold lower value than the designated elimination half-life and amounts to only 3.4 h. The concentration of the drug in the milk drop relatively quickly and the process is very dynamic.