No 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.

The effects of pneumonia on the pharmacokinetics of chloramphenicol, lincomycin, and oxytetracycline were evaluated in two-month-old calves. Pneumonia was induced by injection of Pasteurella haemolytica cultures directly through the thoracic wall into each lung. Six days prior to induction of pneumonia, the antibiotics were administered in a single i.v. dose. The antibiotics were administered again 48 (i.v.), 60 and 72 h (i.m.) following injection of P. haemolytica. The pharmacokinetics of chloramphenicol (25 mg/kg) and lincomycin (10 mg/kg) were not significantly different in calves with pneumonia. The hybrid rate constant beta for oxytetracycline was increased in calves with pneumonia from 0.0034 +/- 0.0003/min to 0.0048 +/- 0.0007/min between 2 h and 8 h. Thus the elimination half-life in serum was shortened from 212.4 +/- 20.3 min to 149.3 +/- 19.5 min. In addition, there was an apparent but not statistically significant decrease in K12 with pneumonia. These findings accentuate the need for observance of 12-h dose intervals with oxytetracycline.

Summary Endotoxins are non‐protein fragments of the cell wall of Gramnegative bacteria. They must be absorbed into the circulation to produce disease and systemic effects are similar, regardless of bacterial source. Absorption of endotoxins occurs in obstructive bowel disease and may play a significant part in determining the severity of the disease. Many of the responses to experimentally administered endotoxin are identical to those of bowel diseases of the horse and include circulatory, haematological and metabolic alterations. Therapeutic approaches are indirect and include many drugs currently employed in equine practice. The agents are directed toward mediators of the disease rather than the endotoxins themselves and include fluids, corticosteroids, anti‐inflammatory drugs, energy sources and vasoactive drugs. The rationale for use and dosages are discussed. Résumé Les endotoxines sont des fragments non protéiques de la paroi cellulaire des bactéries Gram‐. Ils doivent être entraînés par la circulation sanguine pour engendrer des maladies et les effets systémiques sont semblables, quelle que soit la source bactérienne. L'absorption d'endotoxines se produit lors d'obstruction intestinale et cela peut jouer une part importante dans la sévérité de la maladie, Bien des résultats faisant suite à l'administration expérimentale d'endotoxines sont identiques à ceux constatés lors d'obstruction intestinale chez le cheval, et comportent des altérations métaboliques, hématologiques et circulatoires. Les démarches thérapeutiques sont indirectes et utilisent de nombreux médicaments d'emploi courant en médecine équine. Les agents thérapeutiques sont utilisés contre les relais de la maladie à défaut de pouvoir agir contre les endotoxines elles mêmes; ils comportent des solutés, des corticostéroîdes, des anti inflammatoires, des sources énergétiques et des agents vaso actifs. On en discute les dosages et l'emploi. Zusammenfassung Endotoxine sind eiweissfreie Fragmente der Zellwand gramnegativer Bakterien. Um Krankheitszeichen hervorrufen zu können, müssen sie in die Zirkulation absorbiert werden, unabhängig von der bakteriellen Quelle. Eine Endotoxinabsorption ergibt sich bei obstruktiven Darmkrankheiten; sie kann den Grad einer Erkrankung signifikant beeinflussen. Viele der mit experimentell verabreichtem Endotoxin ausgelösten Zeichen sind mit denjenigen von Darmerkrankungen des Pferdes identisch. Sie umfassen zirkulatorische, haematologische und metabolische Veränderungen. Die Behandlung erfolgt indirekt mit vielen der in der Pferdepraxis üblichen Medikamente. Die Mittel richten sich gegen die Krankheitsmediatoren und nicht gegen die Endotoxine selbst; sie umfassen Flüssigkeiten, Corticosteroide, Entzündungshemmer, Energiespender und vasoaktive Substanzen. Die Rationalität von Gebrauch und Dosierungen wird besprochen.

The pharmacokinetics of three antibiotics--gentamicin, neomycin and oxytetracycline were determined in newborn calves. The kinetic determinations, using two-compartment open models, were made at increasing ages from 1 day to 42 days and compared with those made from older calves (250+ days). Although all three antibiotics are eliminated unchanged primarily by glomerular filtration, there were marked differences in the development of elimination processes for individual drugs. The pharmacokinetics of neomycin were not influenced by age. Although the elimination half-life of gentamicin appeared to decrease with age, the changes were not significant and were due to an increased elimination rate in only one calf. There was no change with age in the remaining three calves. Oxytetracycline elimination was significantly reduced in newborn calves. This was exemplified by a decrease in the half-life of elimination t1/2 (beta) from 672.5 +/- 99.4 in the newborn to 385.6 +/- 76.8 at 6 weeks of age, and 377.3 +/- 40.8 min in the 250-day-old calf. These changes were consistent in all four calves. The rate of elimination remained low for the first 4 weeks of life. The volume of distribution Vd, area was not changed after the first week of life. Based on pharmacokinetic changes, an adjustment of dosage is indicated for oxytetracycline in the newborn calf as compared to the older calf or adult.