Effect of Pasteurella haemolytica infection on the distribution of sulfadiazine and trimethoprim into tissue chambers implanted subcutaneously in cattle

A study was designed to determine the effect of Pasteurella haemolytica infection on the rate and extent of penetration of sulfadiazine and trimethoprim into tissue chambers implanted SC in cattle. Thermoplastic tissue chambers were implanted SC in 6 calves. At 35 days after implantation, sulfadiazine (25 mg/kg of body weight) and trimethoprim (5 mg/kg) were administered IV to 5 of the calves. Chamber fluid and blood samples were collected from each animal at various time intervals for 24 hours after administration. Ten days later, all chambers were inoculated with P haemolytica serotype 1. At 36 hours after inoculation, a second pharmacokinetic study was conducted, using sulfadiazine and trimethoprim. Drug doses and sampling schedules were identical to those used prior to inoculation. A histologic study of infected chamber tissue was conducted, using the calf not included in the pharmacokinetic studies. Disposition curves of antimicrobials in serum and chamber fluid were well described by 2-compartment and 1-compartment pharmacokinetic models, respectively. Inoculation of P haemolytica into tissue chambers was accompanied by marked changes in the composition of chamber fluid. Increased total protein and albumin concentrations, decreased pH, and disruption of chamber tissue vasculature were associated with a significant increase in the penetration of sulfadiazine and trimethoprim into infected tissue chambers, compared with that in noninfected chambers. This increased penetration was accompanied by increases in the apparent volume of distribution for sulfadiazine and trimethoprim.