The objectives of this study were to evaluate efficacy of a 2-dose regimen of ceftiofur crystalline free acid sterile suspension (CCFA-SS) for treatment of acute metritis in lactating dairy cows under field conditions and to provide additional safety and injection site tolerance data for injections at the base of the ear. Cows at 15 dairies with rectal temperature ≥ 39.5°C and fetid uterine discharge ≤ 10 d postcalving were randomly assigned by blocks of 2, based on order of entry and without regard to parity, to treatment with saline (1.5 mL/45.5 kg of body weight, n=509) or CCFA-SS (6.6 mg of ceftiofur equivalents/kg of body weight, n=514). Treatments were administered by subcutaneous injection in the posterior aspect of the ear where it attaches to the head; the first dose was administered on study d 0 and the second dose was administered in the contra lateral ear on study d 3. Rectal temperatures were recorded on study d 1 to 4 and 5 or 6 and cows were clinically evaluated daily from study d 1 to 13. Cows that exhibited increased adverse clinical signs of poor health or complications associated with metritis were categorized as a treatment failure and administered escape therapy. Each cow received a veterinary physical examination on study d 5 or 6 to determine if she should be removed from the study and on study d 14 to determine clinical cure or failure to cure. Clinical cure was defined as rectal temperature <39.5°C and non-fetid and purulent or mucopurulent discharge on study d 14 and no escape therapy administered. The injection procedure was scored after each injection (study d 0 and 3) and injection sites and ear carriage were scored on study d 5 or 6, 14, and 57±3. Of the 1,023 cows enrolled, 7 were completely censored due to protocol deviations and 34 were removed for protocol deviations or medical conditions not related to metritis. Clinical cure rate was higher for CCFA-SS than for saline (74.3 vs. 55.3%) and rectal temperatures for each of study d 1 to 5 or 6 were lower for CCFA-SS than saline. Injection procedure indices showed that CCFA-SS could be practically and safely administered using commercial dairy facilities. Although injection site scores were higher for CCFA-SS than saline at study d 5 or 6 and 14, ≥98.6% of ears were normal on d 57±3. Thus, a 2-dose treatment with CCFA-SS given 72h apart increased metritis clinical cure rate and was well tolerated in dairy cows.

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The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week.

Tulathromycin had immunomodulatory effects in leukocytes in vitro and anti-inflammatory effects in pigs in experimental models of A pleuropneumoniae infection and nonmicrobial-induced pulmonary inflammation. These data suggested that in addition to its antimicrobial properties, tulathromycin may dampen severe proinflammatory responses and drive resolution of inflammation in pigs with microbial pulmonary infections.