ATCvet code: QJ01DD90
Pharmacodynamics
Ceftiofur is a late generation cephalosporin, which is active against many Gram-positive and Gram-negative bacteria. Ceftiofur inhibits the bacterial cell wall synthesis, thereby exerting bactericidal properties.
β-lactams act by interfering with synthesis of the bacterial cell wall. Cell wall synthesis is dependent on enzymes that are called penicillin-binding proteins (PBP's). Bacteria develop resistance to cephalosporins by four basic mechanisms: 1) altering or acquiring penicillin binding proteins insensitive to an otherwise effective β-lactam; 2) altering the permeability of the cell to β-lactams; 3) producing β-lactamases that cleave the β-lactam ring of the molecule, or 4) active efflux.
Some β-lactamases, documented in Gram-negative enteric organisms, may confer elevated MICs to varying degrees to third and fourth generation cephalosporins, as well as penicillins, ampicillins, β-lactam inhibitor combinations, and first and second generation cephalosporins.
Ceftiofur is active against the following microorganisms which are involved in respiratory diseases in pigs: Pasteurella multocida, Actinobacillus pleuropneumoniae and Streptococcus suis. Bordetella bronchiseptica is intrinsically non-susceptible to ceftiofur.
It is also active against bacteria involved in respiratory disease in cattle: Pasteurella multocida, Mannheimia haemolytica (former Pasteurella haemolytica), Histophilus somni (former Haemophilus somnus); bacteria involved in acute bovine foot rot (interdigital necrobacillosis) in cattle: Fusobacterium necrophorum, Bacteroides melaninogenicus (Porphyromonas asaccharolytica); and bacteria associated with acute post-partum (puerperal) metritis in cattle: Escherichia coli, Arcanobacterium pyogenes and Fusobacterium necrophorum.
The following Minimum Inhibitory Concentrations (MIC) have been determined for ceftiofur in European isolates of target bacteria, isolated from diseased animals:
Pigs |
Organism (number of isolates) | MIC range (mcg/ml) | MIC90 (mcg/ml) |
Actinobacillus pleuropneumoniae (157) | 0.008 - 2 | 0.03 |
Pasteurella multocida (152) | ≤ 0.002 - 0.06 | 0.004 |
Streptococcus suis (151) | 0.06 - ≥16 | 0.5 |
Cattle |
Organism (number of isolates) | MIC range (mcg/ml) | MIC90 (mcg/ml) |
Mannheimia haemolytica (149) | ≤ 0.002 - 0.12 | 0.015 |
Pasteurella.multocida (134) | ≤ 0.002 - 0.015 | 0.004 |
Histophilus somni (66) | ≤ 0.002 - 0.008 | 0.004 |
Truperella pyogenes (35) | 0.25 - 4 | 2 |
Escherichia coli (209) | 0.13 - 2 | 0.5 |
Fusobacterium necrophorum (67) (isolates from cases of foot rot) | ≤ 0.06 - 0.13 | ND |
Fusobacterium necrophorum (2) (isolates from cases of acute metritis) | ≤ 0.03 - 0.06 | ND |
ND: not determined.
The following breakpoints are recommended by CLSI for bovine and porcine respiratory pathogens currently on the label for the veterinary medicinal product:
Zone Diameter (mm) | MIC (mcg/ml) | Interpretation |
≥ 21 | ≤ 2.0 | (S) Susceptible |
18 - 20 | 4.0 | (I) Intermediate |
≤ 17 | ≥ 8.0 | (R) Resistant |
No breakpoints have been determined to date for the pathogens associated with foot rot or acute post-partum metritis in cows.
Pharmacokinetics
After administration, ceftiofur is quickly metabolised to desfuroylceftiofur, the principal active metabolite.
Desfuroylceftiofur has an equivalent anti-microbial activity to ceftiofur against the bacteria involved in respiratory disease in animals. The active metabolite is reversibly bound to plasma proteins. Due to transportation with these proteins, the metabolite concentrates at a site of infection, is active and remains active in the presence of necrotic tissue and debris.
In pigs given a single intramuscular dose of 3 mg/kg body weight (bw), maximum plasma concentrations of 11.8 ± 1.67 mcg/ml were reached after 1 hour; the terminal elimination half-life (t½) of desfuroylceftiofur was 16.7 ± 2.3 hours. No accumulation of desfuroylceftiofur has been observed after a dose of 3 mg ceftiofur/kg bw/day administered daily over 3 days.
The elimination occurred mainly via the urine (more than 70 %). Average recoveries in faeces accounted for approximately 12-15 % of the drug.
Ceftiofur is completely bioavailable following intramuscular administration.
After a single 1 mg/kg dose given subcutaneously to cattle, maximum plasma levels of 2.85 ± 1.11 mcg/ml are reached within 2 hours after administration. In healthy cows, a Cmax of 2.25 ± 0.79 mcg/ml was reached in the endometrium 5 ± 2 hours after a single administration. Maximum concentrations reached in caruncles and lochiae of healthy cows were 1.11 ± 0.24 mcg/ml and 0.98 ± 0.25 mcg/ml, respectively.
The terminal elimination half-life (t½) of desfuroylceftiofur in cattle is 11.5 ± 2.57 hours. No accumulation was observed after a daily treatment over 5 days. The elimination occurred mainly via the urine (more than 55 %); 31 % of the dose was recovered in the faeces.
Ceftiofur is completely bioavailable following subcutaneous administration.