Ceftiofur

Cephalosporin antibiotic Beta-lactam antimicrobial

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog SC 2.2 mg/kg q24h Duration: 5-7 days
Notes: For UTI and skin infections. Adjust based on culture and sensitivity.
Cat SC 2.2 mg/kg q24h Duration: 5-7 days
Notes: For UTI and skin infections. Use cautiously in renal impairment.
Horse IM 2.2 mg/kg q24h Duration: 5-7 days
Notes: For respiratory infections. Administer deep IM.
Cattle SC 1.1-2.2 mg/kg q24h Duration: 3-5 days
Notes: For BRD, foot rot, and metritis. Approved dose for BRD is 1.1-2.2 mg/kg q24h for 3-5 days.
Cattle SC 6.6 mg/kg single dose Duration: Once
Notes: For BRD as a single-dose regimen (e.g., Excede).
Swine IM 3-5 mg/kg q24h Duration: 3 days
Notes: For respiratory disease. Administer in neck muscle.
Sheep/Goat IM 1-2 mg/kg q24h Duration: 3-5 days
Notes: Extra-label use; observe withdrawal times.

Clinical Indications & Species Uses

General Indications
  • Treatment of bacterial infections caused by susceptible Gram-positive and Gram-negative organisms
Dog (Canine)
  • Treatment of urinary tract infections (UTI) caused by susceptible bacteria
  • Treatment of skin and soft tissue infections
  • Treatment of respiratory tract infections
Cat (Feline)
  • Treatment of urinary tract infections (UTI) caused by susceptible bacteria
  • Treatment of skin and soft tissue infections
  • Treatment of respiratory tract infections
Horse (Equine)
  • Treatment of respiratory tract infections caused by Streptococcus equi subsp. zooepidemicus
  • Treatment of urinary tract infections
  • Treatment of septicemia
  • Treatment of metritis
Cattle (Bovine)
  • Treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni
  • Treatment of acute bovine interdigital necrobacillosis (foot rot) caused by Fusobacterium necrophorum and Bacteroides melaninogenicus
  • Treatment of acute metritis associated with Escherichia coli, Arcanobacterium pyogenes, and Fusobacterium necrophorum
Small Ruminants (Sheep / Goat)
  • Treatment of respiratory disease in sheep and goats
  • Treatment of foot rot in sheep and goats
  • Treatment of metritis in sheep and goats

Pharmacology & Mechanism of Action

Drug Class: Cephalosporin antibiotic | Pharmacological Group: Beta-lactam antimicrobial

Mechanism of Action: Ceftiofur is a third-generation cephalosporin that exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. It binds to penicillin-binding proteins (PBPs) located on the bacterial cell wall, interfering with the transpeptidation step of peptidoglycan synthesis. This leads to weakening of the cell wall and eventual cell lysis, particularly during active bacterial replication. Ceftiofur is stable against many beta-lactamases, enhancing its activity against a broad spectrum of Gram-positive and Gram-negative bacteria.

Pharmacodynamics: Ceftiofur exhibits time-dependent bactericidal activity. Its efficacy is optimized when drug concentrations exceed the minimum inhibitory concentration (MIC) for a significant portion of the dosing interval. It has a broad spectrum of activity against many veterinary pathogens, including Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, Escherichia coli, Salmonella spp., Streptococcus spp., Staphylococcus spp., and various anaerobes. It is generally ineffective against methicillin-resistant staphylococci, enterococci, and some extended-spectrum beta-lactamase (ESBL)-producing bacteria.

⚑ Pharmacokinetics Summary

Absorption: Ceftiofur is poorly absorbed orally; therefore, it is administered parenterally. After intramuscular (IM) or subcutaneous (SC) injection, absorption is rapid and complete. In cattle, peak plasma concentrations are achieved within 1-2 hours. In swine, IM injection results in peak concentrations within 1-3 hours. In horses, IM administration yields peak concentrations within 1-2 hours.
Distribution: Ceftiofur is widely distributed in body tissues and fluids. It penetrates well into pleural, peritoneal, and synovial fluids. It crosses the blood-brain barrier poorly unless inflammation is present. Protein binding is moderate to high, ranging from 50-90% depending on species. It is distributed into milk, but concentrations are low.
Metabolism: Ceftiofur is rapidly metabolized to desfuroylceftiofur, which retains antimicrobial activity. This metabolite is further conjugated to form stable, inactive metabolites. The liver and kidney are involved in metabolism.
Excretion: The primary route of excretion is renal, with both active and inactive metabolites eliminated in urine. Fecal excretion also occurs via biliary elimination. In cattle, the elimination half-life is approximately 2.5-5 hours for the parent drug, but the active metabolite has a longer half-life.
Half-Life: Cattle: 2.5-5 hours (parent drug); 12-16 hours (active metabolites). Swine: 8-14 hours (active metabolites). Horses: 2-3 hours (parent drug). Dogs: 1-2 hours (parent drug).
Bioavailability: Oral bioavailability is low (<10%). IM and SC administration result in near-complete bioavailability (90-100%).
Protein Binding: Cattle: ~50-70%; Swine: ~70-90%; Horses: ~50-60%; Dogs: ~60-80%.

Available Formulations & Strengths

Injectable Suspension 50 mg/mL, 100 mg/mL (IM, SC)
Powder for Injection 1 g, 4 g vials (IM, SC)
Intramammary Infusion 125 mg per syringe (Intramammary)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to ceftiofur or other cephalosporins
  • Known hypersensitivity to beta-lactam antibiotics (e.g., penicillins) due to cross-reactivity
  • Do not use in animals with a history of severe allergic reactions to beta-lactams
Warnings & Clinical Precautions:
  • Use with caution in animals with renal impairment; dose adjustment may be necessary.
  • Prolonged use may result in overgrowth of non-susceptible organisms (e.g., Clostridium difficile).
  • Avoid extra-label use in food animals without veterinary supervision and observance of withdrawal times.
  • In horses, IM injection may cause local tissue irritation; rotate injection sites.
  • In cattle, subcutaneous injection may cause local swelling at injection site.
  • Do not administer intravenously (IV) as it may cause severe injection site reactions.
  • Use in animals with a history of gastrointestinal disease (e.g., colitis) with caution.
  • Ceftiofur is not effective against methicillin-resistant Staphylococcus aureus (MRSA) or enterococci.

Adverse Effects & Reactions

Common:

  • Injection site swelling or pain
  • Local tissue irritation
  • Diarrhea
  • Nausea or vomiting (rare in animals)

Serious / Severe:

  • Anaphylaxis (rare)
  • Clostridium difficile-associated diarrhea
  • Renal toxicity (rare)
  • Blood dyscrasias (rare)

Rare:

  • Seizures (with high doses)
  • Hepatotoxicity
  • Allergic skin reactions

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Aminoglycosides (e.g., gentamicin) Potential for additive nephrotoxicity; monitor renal function. Moderate
Probenecid May increase ceftiofur concentrations by decreasing renal tubular secretion. Mild
Bacteriostatic antibiotics (e.g., tetracyclines, macrolides) May antagonize the bactericidal effect of ceftiofur; avoid concurrent use. Moderate
Loop diuretics (e.g., furosemide) May increase risk of nephrotoxicity. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Gastrointestinal upset (vomiting, diarrhea)
  • Neurological signs (tremors, seizures) in severe cases
  • Nephrotoxicity
  • Injection site reactions

Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce emesis if recent oral ingestion (though oral absorption is poor). Monitor renal function and provide fluid therapy. In severe cases, consider anticonvulsants for seizures. Discontinue drug and provide supportive care.

Food Animal Withdrawal Times

πŸ₯© Meat: 4 daysπŸ₯› Milk: 0 days

Withdrawal times vary by formulation and country. For cattle, meat withdrawal is 4 days for the injectable suspension (e.g., Naxcel) and 0 days for milk. For swine, meat withdrawal is 4 days. For sheep and goats, extra-label use requires extended withdrawal times; consult a veterinarian. No egg withdrawal is established for poultry as it is not approved.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25Β°C (68-77Β°F); protect from freezing.

Light Sensitivity: Light-sensitive β€” protect from direct exposure.

Handling & Special Conditions: Protect from light. Shake well before use. Do not mix with other drugs in the same syringe.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for use in cattle, swine, horses, dogs, and cats. Specific formulations have FDA approval for certain indications.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with veterinary supervision, but requires extended withdrawal times. In the EU, extra-label use is restricted. Always follow label directions.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Ceftiofur is a valuable third-generation cephalosporin in veterinary medicine due to its broad spectrum and low toxicity. It is particularly useful for respiratory infections in cattle and swine. It is not effective against MRSA or enterococci, so culture and sensitivity testing is recommended. In food animals, adherence to withdrawal times is critical. In companion animals, it is often used for UTIs and skin infections when other antibiotics fail. It is generally well-tolerated, but injection site reactions are common. Use with caution in animals with renal impairment. For optimal efficacy, administer at the correct dose and frequency to maintain therapeutic concentrations.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)