Response of Pasteurella haemolytica to erythromycin and dexamethasone in calves with established infection

Cyril R. Clarke From the Departments of Physiological Sciences (Clarke, Burrows) and Medicine & Surgery (Barron), College of Veterinary Medicine, and the Department of Botany and Microbiology, College of Arts and Sciences (Ayalew), Oklahoma State University, Stillwater, OK 74078.

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Selwyn J. Barron From the Departments of Physiological Sciences (Clarke, Burrows) and Medicine & Surgery (Barron), College of Veterinary Medicine, and the Department of Botany and Microbiology, College of Arts and Sciences (Ayalew), Oklahoma State University, Stillwater, OK 74078.

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Sahlu Ayalew From the Departments of Physiological Sciences (Clarke, Burrows) and Medicine & Surgery (Barron), College of Veterinary Medicine, and the Department of Botany and Microbiology, College of Arts and Sciences (Ayalew), Oklahoma State University, Stillwater, OK 74078.

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George E. Burrows From the Departments of Physiological Sciences (Clarke, Burrows) and Medicine & Surgery (Barron), College of Veterinary Medicine, and the Department of Botany and Microbiology, College of Arts and Sciences (Ayalew), Oklahoma State University, Stillwater, OK 74078.

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 DVM, PhD

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Summary

A subcutaneous soft tissue infection model in calves was used to study the in vivo response of Pasteurella haemolytica to erythromycin and dexamethasone. Two tissue chambers were implanted sc in each of 12 calves. At 45 days after implantation, all tissue chambers were inoculated with an erythromycin-sensitive strain of P haemolytica. Starting 24 hours after inoculation, calves were allotted to 4 groups of equal size and a 2 × 2-factorial arrangement of treatments was applied: 3 calves were given erythromycin (30 mg/kg of body weight, im, for 5 days), 3 calves were given dexamethasone(0.05 mg/kg, im, for 2 days), 3 calves were given erythromycin and dexamethasone, and the remaining calves served as nontreated controls. Chamber fluids were tested daily, and the response to treatment was measured. Neither erythromycin nor dexamethasone affected viability or growth of bacteria within tissue chambers. Dexamethasone had no effect on the influx of neutrophils into infected chambers. Despite repeated administration of a high dose of erythromycin and attainment of adequate concentration in serum, erythromycin concentration in chamber fluids did not exceed the minimal inhibitory concentration established in vitro. These results indicate that the clinical efficacy of erythromycin against P haemolytica sequestered in consolidated pneumonic lesions may not be well correlated with predictions based on serum pharmacokinetic and in vitro susceptibility data.

Summary

A subcutaneous soft tissue infection model in calves was used to study the in vivo response of Pasteurella haemolytica to erythromycin and dexamethasone. Two tissue chambers were implanted sc in each of 12 calves. At 45 days after implantation, all tissue chambers were inoculated with an erythromycin-sensitive strain of P haemolytica. Starting 24 hours after inoculation, calves were allotted to 4 groups of equal size and a 2 × 2-factorial arrangement of treatments was applied: 3 calves were given erythromycin (30 mg/kg of body weight, im, for 5 days), 3 calves were given dexamethasone(0.05 mg/kg, im, for 2 days), 3 calves were given erythromycin and dexamethasone, and the remaining calves served as nontreated controls. Chamber fluids were tested daily, and the response to treatment was measured. Neither erythromycin nor dexamethasone affected viability or growth of bacteria within tissue chambers. Dexamethasone had no effect on the influx of neutrophils into infected chambers. Despite repeated administration of a high dose of erythromycin and attainment of adequate concentration in serum, erythromycin concentration in chamber fluids did not exceed the minimal inhibitory concentration established in vitro. These results indicate that the clinical efficacy of erythromycin against P haemolytica sequestered in consolidated pneumonic lesions may not be well correlated with predictions based on serum pharmacokinetic and in vitro susceptibility data.

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