Pharmacotherapeutic group: Antibacterials for systemic use, ATCvet code: QJ01DD90.
Pharmacodynamic properties
Ceftiofur is a late generation cephalosporin, which is active against Gram-positive and Gram-negative bacteria. Like all beta-lactam antibiotics, ceftiofur inhibits bacterial cell wall synthesis, thereby exerting bactericidal properties.
Cell wall synthesis is dependent on enzymes that are called penicillin-binding proteins (PBP´s). Bacteria may develop resistance to cephalosporins by 1) having penicillin binding proteins insensitive to an otherwise effective β-lactam; 2) altering cell permeability to β-lactams; 3) producing β-lactamases that cleave the β-lactam ring of the antibiotic, or 4) active efflux.
Some β-lactamases, documented in Gram-negative enteric organisms, may lead to varying degrees of cross resistance between cephalosporins, as well as with penicillins, ampicillins and β-lactam inhibitor combinations.
Ceftiofur is active against the following microorganisms which are involved in respiratory diseases in swine: 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, Histophillus somni; bacteria involved in acute bovine foot rot (interdigital necrobacillosis): Fusobacterium necrophorum, Bacteroides melaninogenicus (Porphyromonas asaccharolyitica); 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:
PIGS |
Organism (number of isolates | MIC range (μg/mL) | MIC 90(μg/mL) |
A. pleuropneumoniae (28) | <0.03* | <0.03 |
Pasteurella multocida (37) | <0.03-0.13 | <0.03 |
Streptococcus suis (495) | <0.03-025 | <0.03 |
CATTLE |
Organism (number of isolates) | MIC range (μg/mL) | MIC 90 (μg/mL) |
Mannheimia spp. (87) | <0.03* | <0.03 |
P.multocida (42) | <0.03-0.12 | <0.03 |
H. Somni (24) | <0.03* | <0.03 |
Arcanobacterium pyogens (123) | <0.03-0.5 | 0.25 |
Escherichia coli (188) | 0.13->32.0 | 0.5 |
Fusobacterium necrophorum (67) | | |
(from cases of foot rot) | <0.06-0.13 | ND |
Fusobacterium necrophorum (2) | | |
(from cases of acute metritis) | <0.03-0.06 | ND |
* No range; all isolates yielded the same value. ND: not determined.
The following breakpoints are recommended by NCCLS for bovine and porcine respiratory pathogens:
Zone Diameter (mm) | MIC (μ/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.
Pharmacokinetic properties
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. It is reversibly bound to plasma proteins and as a result, the metabolite concentrates at sites of infection. It remains active in the presence of necrotic tissue and debris.
Pigs
A single intramuscular dose of the product at 3 mg ceftiofur/kg body weight resulted in mean Cmax of approximately 9 microgram/mL after about 1 hour. The terminal elimination half-life (t1/2) of desfuroylceftiofur was about 23 hours. No accumulation of desfuroylceftiofur has been observed after a dose of 3 mg ceftiofur/kg bw/day administered daily over 3 days.
Elimination occurs mainly via the urine (more than 70%); 12-15 % is eliminated via faeces.
Ceftiofur is completely bioavailable following intramuscular administration.
Cattle
A single subcutaneous dose of the product at 1 mg ceftiofur/kg resulted in mean Cmax of approximately 2 microgram/mL after about 2.5 hours. After administration of the product, the terminal elimination half-life (t1/2) of desfuroylceftiofur in cattle is approximately 18 hours.
In other studies in healthy cows, a mean Cmax of approximately 2.25 microgram/mL was reached in the endometrium about 5 hours after a single administration of cefiofur. Maximum mean concentrations reached in caruncles and lochiae of healthy cows were about 1 microgram/mL.
No accumulation of desfuroylceftiofur has been observed after a daily treatment of ceftiofur over 5 days. Elimination occurs mainly via the urine (more than 55%). 31% is eliminated in the faeces.
Ceftiofur is completely bioavailable following subcutaneous administration.