Response of Pasteurella haemolytica to erythromycin and dexamethasone in calves with established infection.
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 x 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.
Clarke
C R
CR
Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
Barron
S J
SJ
Ayalew
S
S
Burrows
G E
GE
D000418:Albumins / Q000032:analysis; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy*; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015194:Diffusion Chambers, Culture; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004917:Erythromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006863:Hydrogen-Ion Concentration; D007273:Injections, Intramuscular / Q000662:veterinary; D007958:Leukocyte Count / Q000662:veterinary; D016978:Mannheimia haemolytica / Q000187:drug effects*; D009504:Neutrophils; D010326:Pasteurella Infections / Q000188:drug therapy / Q000662:veterinary*; D014018:Tissue Distribution
D000418:Albumins; D004917:Erythromycin; D003907:Dexamethasone