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Pharmacological particulars
Pharmacotherapeutic group: Antiinfectives for systemic use, amoxicillin. ATCvet code: QJ01CA04
Pharmacodynamic properties
Amoxicillin is a broad-spectrum antibiotic of the amino-penicillin family with close structural relationship to ampicillin.
Amoxicillin is a bactericide and is active against Gram-positive and Gram-negative bacteria. It inhibits the synthesis and reparation of the bacterial mucopeptide cell wall.
Amoxicillin is a semisynthetic penicillin and susceptible to the action of bacterial beta-lactamases.
Amoxicillin is a time-dependent antibiotic.
Amoxicillin is active against the following microorganisms which are involved in respiratory diseases in cattle: Mannheimia haemolytica and Pasteurella multocida.
Amoxicillin is also active against Pasteurella multocida that is involved in respiratory diseases in pig.
The following Minimum Inhibitory Concentrations (MIC) have been determined for amoxicillin in European isolates (France, United Kingdom, Denmark, Germany, Italy, Czech Republic, and Spain) collected from diseased animals between 2009 to 2012:
Bacteria species
Origin
Nb of strains
MIC of amoxicillin (µg/mL)
Range
MIC50
MIC90
Pasteurella multocida
Cattle
76
0.0312 – 4
0.2
0.3
Pig
89
0.125 – 2
0.2
0.3
Mannheimia haemolytica
Cattle
59
0.125 – 0.5
0.15
0.2
The following amoxicillin breakpoints are recommended by the Comité de l'Antibiogramme of the Société Française de Microbiologie (SFM): ≤ 4 μg/mL (susceptible) and > 16 μg/mL (resistant)
Mechanism of action:
The antimicrobial mechanism of action consists of the inhibition of the biochemical process of bacterial wall synthesis, through a selective and irreversible blockade of several enzymes, in particular transpeptidases, endopeptidases and carboxypeptidases. In susceptible bacteria, impairment of cell wall synthesis particularly during multiplication leads to lysis of the bacteria.
Bacteria which generally present resistance to amoxicillin are:
- Staphylococcus species producing penicillinase,
- Enterobacteria such as Klebsiella spp., Enterobacter spp., Proteus spp. and Pseudomonas aeruginosa.
Bacterial resistance towards amoxicillin is primarily mediated through ß-lactamases which inactivate the antimicrobial by hydrolysis of the ß-lactam ring. Bacterial ß-lactamases can be codified in plasmids or in constituents of the bacterial chromosome.
These beta-lactamases are extracellular in Gram-positive bacteria (Staphylococcus aureus) whereas they are located in the periplasmic space in Gram-negative bacteria.
Gram-positive bacteria can produce beta-lactamases in large quantities. These enzymes are codified in plasmids, which can be transferred to other bacteria.
Gram-negative bacteria produce different types of beta-lactamases, which remain in the periplasmic space and which are codified in the chromosome or in the plasmid.
Complete cross resistance exists between amoxicillin and other penicillins, in particular other aminopenicillins.
Pharmacokinetic particulars
In cattle Cmax (3.45 µg/ml) is reached 2.45 hours after intramuscular administration. In pigs Cmax (3.54 µg/ml) is reached 2 hours after intramuscular administration.
Amoxicillin is mainly distributed to the extra-cellular compartment. Its distribution into tissues is facilitated by its low degree of plasma protein binding (17%). Concentrations in pulmonary, pleural and bronchial tissues are similar to plasma concentrations. Amoxicillin diffuses into pleural and synovial fluid and into lymphatic tissue.
Amoxicillin is biotransformed in the liver by hydrolysis of the ß-lactam ring leading to inactive penicilloic acid (20%).
Amoxicillin is mainly excreted in active form via the kidneys, and secondarily by the biliary route and through milk.