Penetration of parenterally administered ceftiofur into sterile vs. Pasteurella haemolytica‐infected tissue chambers in cattle

Abstract

The effect of bacterial infection on antibiotic activity and penetration of parenterally administered ceftiofur into implanted tissue chambers was studied in cattle. Tissue chambers were implanted subcutaneously in the paralumbar fossae of eight calves (256-290 kg body weight). Approximately 80 days after implantation, the two chambers on one side of each animal were inoculated with Pasteurella haemolytica (10(6) CFU/chamber). Eighteen hours after inoculation, ceftiofur sodium was administered intravenously (5 mg/kg) to each of the calves. Non-infected chamber fluid, infected chamber fluid and heparinized blood samples were collected immediately before and at 1, 3, 6, 12 and 24 h after drug administration. Concentrations of ceftiofur and desfuroylceftiofur metabolites and ceftiofur-equivalent microbiological activity were measured by high-pressure liquid chromatography and microbiological assay respectively. Concentrations of ceftiofur and desfuroylceftiofur metabolites and anti-microbial activity in P. haemolytica-infected tissue chambers were significantly higher than those in non-infected tissue chambers at all sampling times, indicating that ceftiofur, regardless of the method used for analysis, localizes at higher concentrations at tissue sites infected with P. haemolytica. Antibiotic activity-concentration ratios were lower in plasma and infected chamber fluid compared with non-infected chamber fluid, suggesting that antibiotic was bound to proteins. However, higher antimicrobial activity in the infected chamber fluid compared with the non-infected chamber fluid, suggests that active drug is reversibly bound to proteins. Protein-bound desfuroylceftiofur may represent a reservoir for release of active drug at the site of infection in the animal.

Penetration of ceftiofur into sterile vs. Mannheimia haemolytica‐infected tissue chambers in beef calves after subcutaneous administration of ceftiofur crystalline free acid sterile suspension in the ear pinna

“…In contrast to mean t 1/2 (5.95 h) and MRT (6.74 h) values estimated after intravenous (i.v.) administration (Clarke et al. , 1996), median estimates of t 1/2 (57.3 h) and MRT (61.5 h) were considerably longer in the present study.…”

“…Evaluation of drug concentrations in interstitial fluid poses significant sampling difficulties. However, several studies have employed perforated tissue chambers implanted s.c. to characterize interstitial fluid drug concentrations in cattle (Clarke et al. , 1993, 1996).…”

Pharmacokinetic profile of Ceftiofur Hydrochloride Injection in lactating Holstein dairy cows

“…In cattle, ceftiofur crystalline free acid sterile suspension is labeled for single s.c. injection at a dose of 6.6 mg/kg of BW in which plasma concentrations are kept at MIC for at least 7.1 days (FDA, ). Because, protein binding of DFC is reversible and protein‐bound DFC acts as a reservoir for release of active drug at the site of infection (Clarke et al., ). This phenomenon may explain the apparent discrepancy between documented clinical efficacy of ceftiofur after once a day dosing in cattle and pharmacokinetic evaluation based on microbiologic assay which suggests rapid disappearance of the drug.…”

Ceftiofur attenuates lipopolysaccharide-induced acute lung injury

“…Ceftiofur is a broad-spectrum third-generation cephalosporin with activity against both Gram-positive and Gram-negative bacteria including β-lactamase producing strains and anaerobes [6,7]. Ceftiofur hydrochloride (ceftiofur) has been approved for treatment against respiratory diseases in many animals [8][9][10][11].…”