Pharmacotherapeutic group: Beta-lactam antibacterials, penicillins, for intramammary use.
Pharmacodynamic properties
Benzylpenicillin is a bactericidal antibiotic belonging to the betalactam group of antibiotics. It inhibits the peptidoglycan synthesis of Gram-positive bacteria. Benzylpenicillin has no effect on dormant/non-growing bacteria or on most of the Gram-negative bacteria.
Mastitis-causing streptococci are commonly susceptible to penicillin. Both Staphylococcus aureus and coagulase-negative staphylococci may synthesise betalactamase. These strains are resistant to penicillin. Penicillin is active against betalactamase-negative bacteria. The MIC values of penicillin to susceptible pathogens are ordinarily smaller than 0.15 μg/ml.
Most resistance results from production of a beta-lactamase, although modifications of PBPs with reduced drug affinity or reduced bacterial permeability are additional and sometimes concurrent mechanisms of intrinsic and acquired resistance to penicillins.
State of resistance of the target pathogens across Europe:
According to European surveillance reports and literature published in 2009-2018 proportion of the strains susceptible/non-resistant to penicillin from the isolates tested varied from 64 to 98 % for S. aureus, from 63 to 73 % for coagulase negative staphylococci and from 97 to 100 % for streptococci. However, although resistance in streptococci is rare, decrease in susceptibility of Streptococcus uberis has been reported.
The resistance situation remained stable throughout 2002-2018.
Clinical MIC Breakpoints according to CLSI Standards have been set for the evaluation of the resistance development.
Clinical breakpoints for Benzylpenicillin procaine on penicillin-susceptible mastitis pathogens (human derived data)
Pathogen | Source: CLSI Standard VET01S |
| Breakpoint (μg/mL) |
| S1 | I3 | R2 |
Staphylococcus aureus | ≤ 0.12 | – | ≥0.25 |
Coagulase negative Staphylococci | ≤ 0.12 | – | ≥0.25 |
Streptococcus agalactiae | ≤ 0.12 | – | – |
Streptococcus dysgalactiae | ≤ 0.12 | – | – |
Streptococcus uberis | ≤ 0.12 | 0.25 - 2 | ≥4 |
1Susceptible, 2Resistant, 3Intermediate
Pharmacokinetic particulars
Penicillin is minimally absorbed from the udder. Mammary oedema and exudate may inhibit the tissue distribution of the penicillin contained in the product. Thus sufficient drug concentrations might not be achieved. In healthy cows, after one dose of the product administered intramammarily the penicillin concentration in milk remained above 0,15 µg/ml for at least 24 h, even when the quarter is emptied at 2 h intervals for a period of 10 h after the administration. Most of the penicillin in the product is excreted in milk unchanged. About 40% of the drug is eliminated in the milk at the first evacuation, and about 10% at the second evacuation. Therefore, about half of the penicillin dose has been eliminated after two milkings. Penicillin absorbed systemically is excreted via the kidneys unchanged.