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A Review Of Ceftiofur Sodium For The Treatment Of Acute Bovine Foot Rot

May. 12, 2021

Ceftiofur, a broad-spectrum cephalosporin, is active against gram-positive and gram-negative pathogens of veterinary importance, including b-lactamase-producing strains.9-12 As with other cephalosporins, ceftiofur is bactericidal in vitro, resulting from inhibition of cell wall synthesis. Ceftiofur can be synthesized in different salt forms. 

The sodium salt of ceftiofur (Naxcel or Excenel Sterile Powder, Pharmacia & Upjohn Animal Health) has been approved worldwide for treatment of respiratory diseases in beef and dairy cattle, swine, and horses. The hydrochloride salt of ceftiofur HCL injection is a ready-to-use formulation approved for treatment of swine and bovine respiratory disease (BRD). Regardless of which ceftiofur salt is administered, dose recovery, drug distribution in tissues, residue concentrations, and metabolites are similar.

 Ceftiofur HCL Injection 5%

Ceftiofur HCL Injection 5%

Ceftiofur is approved in the United States and Europe for treatment of BRD associated with Mannheimia haemolytica (formerly Pasteurella haemolytica), Pasteurella multocida, and Haemophilus somnus.13,14 In the United States, the dosage for both ceftiofur sodium and ceftiofur hydrochloride is 1.1 to 2.2 mg ceftiofur equivalents (CE)/kg once daily for 3 to 5 days. 

In Europe, the dosage for both salts is 1 mg CE/kg BW for 3 days. Investigation of the in vitro activity of ceftiofur sodium against obligatory anaerobic bacteria of veterinary importance, including F. necrophorum isolated from bovine liver abscesses and foot rot, revealed ceftiofur was highly active against this organism, with an MIC90 of 0.25 µg/ml or less.12 In a second study, 38 isolates of F. necrophorum all had an MIC ranging from 0.016 to 0.062 µg ceftiofur/ml.15


Experience with BRD therapy indicated ceftiofur was very safe when administered to cattle, including lactating dairy cows, although ceftiofur should not be given to animals previously found to be hypersensitive to this compound. This experience also afforded the opportunity to monitor for the emergence of resistance in respiratory pathogens. The absence of resistance to ceftiofur by target pathogens (M. haemolytica, P. multocida, and H. somnus) has been demonstrated in a number of studies since 1988, when the drug was first marketed.16-18 Preslaughter withdrawal time for ceftiofur is 0 to 8 days and milk discard time is 0 to 2 days, depending on the country.


To establish the efficacy and optimal dose for ceftiofur in the treatment of foot rot, seven well-controlled studies were conducted before approval was obtained for the use of ceftiofur for treatment of bovine foot rot. These seven studies included two dosage titration studies that first evaluated the model's suitability for testing of therapeutic regimens and established the time for treatment after challenge and secondly evaluated two dosage levels for ceftiofur when treatment was initiated immediately after the onset of clinical signs of disease. 

After determining that 1.0 mg CE/kg was efficacious against foot rot in these preliminary trials, that dosage was subsequently compared with a placebo and a positive control (oxytetracycline) for both induced and naturally occurring foot rot in dairy and beef cattle at multiple locations in the United Kingdom, United States, Canada, and France under a wide variety of management conditions. Ceftiofur hydrochloride was used in one study; all others used ceftiofur sodium. Ceftiofur was given by IM injection in all but one (dosage titration) study, in which the product was given SC. Both routes of injection have been determined to be interchangeable with regard to efficacy and target animal and human safety.