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Abstract

Objective—To determine disposition kinetics of amikacin in neonatal foals administered high doses at extended intervals.

Animals—7 neonatal foals.

Procedure—Amikacin was administered (21 mg/kg, IV, q 24 h) for 10 days. On days 1, 5, and 10, serial plasma samples were obtained for measurement of amikacin concentrations and determination of pharmacokinetics.

Results—Mean ± SD peak plasma concentrations of amikacin extrapolated to time 0 were 103.1 ± 23.4, 102.9 ± 9.8, and 120.7 ± 17.9 µg/mL on days 1, 5, and 10, respectively. Plasma concentrations at 1 hour were 37.5 ± 6.7, 32.9 ± 2.6, and 30.6 ± 3.5 µg/mL; area under the curve (AUC) was 293.0 ± 61.0, 202.3 ± 40.4, and 180.9 ± 31.2 (µg · h)/mL; elimination half-life (t1/2β) was 5.33, 4.08, and 3.85 hours; and clearance was 1.3 ± 0.3, 1.8 ± 0.4, and 2.0 ± 0.3 mL/(min · kg), respectively. There were significant increases in clearance and decreases in t1/2β, AUC, mean residence time, and plasma concentrations of amikacin at 1, 4, 8, 12, and 24 hours as foals matured.

Conclusions and Clinical Relevance—Once-daily administration of high doses of amikacin to foals resulted in high peak plasma amikacin concentrations, high 1-hour peak concentrations, and large values for AUC, consistent with potentially enhanced bactericidal activity. Age-related findings suggested maturation of renal function during the first 10 days after birth, reflected in enhanced clearance of amikacin. High-dose, extended-interval dosing regimens of amikacin in neonatal foals appear rational, although clinical use remains to be confirmed. (Am J Vet Res 2004;65:473–479)

Full access
in American Journal of Veterinary Research

Summary

The medical records of 25 horses with intra-abdominal neoplasms and 15 horses with intra-abdominal abscesses were reviewed. Common clinical signs of disease observed by owners of horses in both groups included anorexia, weight loss, fever, signs of colic, and depression. Clinical laboratory abnormalities included leukocytosis, hyperfibrinogenemia, hypoalbuminemia, and hypocalcemia. There was considerable overlap of laboratory test results within and between the 2 groups of horses. Peritoneal fluid was classified as an exudate in 12 of 15 horses with intra-abdominal abscesses and in 14 of 25 horses with intra-abdominal neoplasms. Cytologic examination of peritoneal fluid yielded an accurate diagnosis in 11 of 25 horses with neoplasia and in 3 of 15 horses with abscesses. A mean number of 1.45 cytologic analyses/horse was needed to diagnose neoplasms in the 11 horses in which the analysis was successful in definitively diagnosing the condition.

Free access
in Journal of the American Veterinary Medical Association

Abstract

Objective

To determine pharmacokinetics and bioavailability of erythromycin base after intragastric administration and erythromycin lactobionate after IV administration to healthy foals and to compare a microbiologic assay with a high-performance liquid chromatography (HPLC) method to determine plasma concentrations of erythromycin A.

Animals

6 healthy foals that were 2 to 4 months old.

Procedure

Foals were given single doses of erythromycin (10 mg/kg of body weight, IV, and 25 mg/kg, intragastrically) in a crossover study. Venous blood samples were obtained at specific times after drug administration, and plasma was harvested for determination of erythromycin concentrations by microbiologic assay and a HPLC method. Pharmacokinetic analysis of plasma concentration-time data was performed, and results derived from each method were compared.

Results

Concentration-time profiles for IV administration were best described by a two-compartment open model. Comparing pharmacokinetic data obtained by the 2 methods revealed substantial differences in results. Values for area under the plasma concentration-time curve and area under the first moment of the curve were substantially higher when determined by the bioassay, indicating overestimation of plasma concentration-time data by this method. The derived rate transfer constants (K21 and Ke1) and mean residence time were significantly different, when determined by the bioassay. Systemic bioavailability of erythromycin base was low in all foals.

Conclusions and Clinical Relevance

The bioassay method overestimated plasma concentrations of erythromycin, compared with the HPLC method. Despite low systemic bioavailability of erythromycin base administered intragastrically, plasma concentrations of erythromycin exceeded, for at least 4 hours, the minimum inhibitory concentration of most Rhodococcus equi isolates. (Am J Vet Res 1999;60:414-419)

Free access
in American Journal of Veterinary Research

Summary

Fifteen isolates of Escherichia coli obtained from the blood and tissues of septic foals had plasmid dna of size ranging from 2.5 to 93 megadaltons. These isolates grew in normal equine serum (serum resistant), a trait previously documented to be expressed by isolates obtained from blood and tissues of septic foals, but not by isolates obtained from the feces of clinically normal horses. Of these isolates, 3 contained conjugal plasmids that encoded resistance to multiple antimicrobial agents linked to serum resistance and, in 1 isolate, to production of aerobactin as well. Serum resistance and production of aerobactin are related to virulence of septicemic E coli from non-equine sources.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine pharmacokinetics and plasma concentrations of erythromycin and related compounds after intragastric administration of erythromycin phosphate and erythromycin estolate to healthy foals.

Animals—11 healthy 2- to 6-month-old foals.

Procedure—Food was withheld from foals overnight before intragastric administration of erythromycin estolate (25 mg/kg of body weight; n = 8) and erythromycin phosphate (25 mg/kg; 7). Four foals received both drugs with 2 weeks between treatments. Plasma erythromycin concentrations were determined at various times after drug administration by use of high-performance liquid chromatography. Maximum plasma peak concentrations, time to maximum concentrations, area under plasma concentration versus time curves, half-life of elimination, and mean residence times were determined from concentration versus time curves.

Results—Maximum peak concentration of erythromycin A after administration of erythromycin phosphate was significantly greater than after administration of erythromycin estolate (2.9 ± 1.1 µg/ml vs 1.0 ± 0.82 µg/ml). Time to maximum concentration was shorter after administration of erythromycin phosphate than after erythromycin estolate (0.71 ± 0.29 hours vs 1.7 ± 1.2 hours). Concentrations of anhydroerythromycin A were significantly less 1 and 3 hours after administration of erythromycin estolate than after administration of erythromycin phosphate.

Conclusions and Clinical Relevance—Plasma concentrations of erythromycin A remained > 0.25 µg/ml (reported minimum inhibitory concentration for Rhodococcus equi) for at least 4 hours after intragastric administration of erythromycin phosphate or erythromycin estolate, suggesting that the recommended dosage for either formulation (25 mg/kg, q 6 h) should be adequate for treatment of R equi infections in foals. (Am J Vet Res 2000;61:914–919)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine effects of prior feeding on pharmacokinetics and estimated bioavailability of orally administered microencapsulated erythromycin base (MEB) in healthy foals.

Animals—6 healthy foals, 3 to 5 months old.

Procedure—Foals were given 2 doses of MEB (25 mg/kg of body weight, PO). One dose was administered after food was withheld overnight, and the other was administered after foals had consumed hay. The study used a crossover design with a 2-week period between doses. Blood was collected via a jugular vein prior to and at specific times after drug administration. Concentrations of erythromycin A and anhydroerythromycin A in plasma were determined, using highperformance liquid chromatography. Results pharmacokinetic analysis of plasma concentration-time data for food-withheld and fed conditions were compared.

Results—Plasma concentrations of erythromycin A for foals were lower after feeding than concentrations when food was withheld. Area under the plasma concentration- time curve, maximum plasma concentration, and estimated bioavailability were greater in foals when food was withheld than when foals were fed. Anhydroerythromycin A was detected in plasma after administration of MEB in all foals.

Conclusions and Clinical Relevance—Foals should be given MEB before they are fed hay. Administration of MEB to foals from which food was withheld overnight apparently provides plasma concentrations of erythromycin A that exceed the minimum inhibitory concentration of Rhodococcus equi for approximately 5 hours. The dosage of 25 mg/kg every 8 hours, PO, appears appropriate. (Am J Vet Res 2000;61:1011–1015)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the efficacy and safety of intra-articular administration of ethyl alcohol for arthrodesis of tarsometatarsal joints in horses.

Animals—8 healthy female horses without lameness or radiographic evidence of tarsal joint osteoarthritis.

Procedure—In each horse, 1 tarsometatarsal joint was treated with 4 mL of 70% ethyl alcohol and the opposite joint was treated with 4 mL of 95% ethyl alcohol. Lameness examinations were performed daily for 2 weeks, followed by monthly evaluations for the duration of the 12-month study. Radiographic evaluations of both tarsi were performed 1 month after injection and every 3 months thereafter. Gross and histologic examinations of the tarsi were undertaken at completion of the study.

Results—Horses had minimal to no lameness associated with the treatments. Radiography revealed that 8 of 16 joints were fused by 4 months after treatment, with significantly more joints fused in the 70% ethyl alcohol group. Fifteen of 16 joints were considered fused at postmortem examination at 12 months. Gross and histologic examinations revealed foci of dense mature osteonal bone spanning the joint spaces. Bony fusion appeared to be concentrated on the dorsolateral, centrolateral, and plantarolateral aspects of the joints. Significant differences were not detected between treatment groups for lameness or pathologic findings.

Conclusions and Clinical Relevance—Administration of ethyl alcohol into the tarsometatarsal joint of healthy horses appeared to facilitate arthrodesis of the joint in a pain-free manner. Results warrant further investigation into the potential use of ethyl alcohol in horses clinically affected with osteoarthritis of the tarsometatarsal and distal intertarsal joints.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine whether foals with pneumonia that were treated with erythromycin, alone or in combination with rifampin or gentamicin, had a higher risk of developing adverse effects, compared with foals treated with trimethoprim-sulfamethoxazole (TMS), penicillin G procaine (PGP), or a combination of TMS and PGP (control foals).

Design—Retrospective study.

Animals—143 foals < 240 days old.

Procedure—Information on age, sex, breed, primary drug treatment, total days of treatment with the primary drug, and whether the foal developed diarrhea, hyperthermia, or respiratory distress was obtained from the medical records. Relative risk (RR) and attributable risk (AR) were calculated to compare risk of adverse reactions between foals treated with erythromycin and control foals.

Results—Only 3 (4.3%) control foals developed diarrhea; none developed hyperthermia or respiratory distress. Foals treated with erythromycin had an 8-fold risk (RR, 8.3) of developing diarrhea, compared with control foals, and increased risks of hyperthermia (AR, 25%) and respiratory distress (AR, 15%).

Conclusion and Clinical Relevance—Results suggest that use of erythromycin to treat foals with pneumonia was associated with an increased risk of diarrhea, hyperthermia, and respiratory distress, compared with use of TMS or PGP. (J Am Vet Med Assoc 2000;217:68–73)

Full access
in Journal of the American Veterinary Medical Association

Objective—

To characterize history, clinical signs, and pathologic findings in horses with histologically confirmed acute hemorrhagic pulmonary infarction and necrotizing pneumonia.

Design—

Retrospective study.

Animals—

21 horses.

Results—

19 of the 21 horses were Thoroughbred racehorses in training. Eighteen horses had had strenuous exercise immediately prior to onset of illness. Fifteen horses had a serosanguineous nasal discharge during hospitalization. Seventeen horses had radiographic evidence of pulmonary consolidation and pleural effusion. Nine of 14 horses had ultrasonographic evidence of large pulmonary parenchymal defects consistent with consolidation. Pleurocentesis yielded a suppurative, serosanguineous effusion in the 14 horses in which it was performed. Bacteria were isolated from all transtracheal aspirates (14) and from 6 of 12 pleural fluid samples. Actinobacillus suis-like organisms and Streptococcus equi subsp zooepidemicus were most commonly isolated. Nineteen horses were hospitalized and treated, Mean duration of treatment was 5 days, and most horses were euthanatized because of secondary complications, continued costs of medical treatment, or poor prognosis for future performance. Pathologic lesions included well-demarcated regions of hemorrhagic pulmonary infarction with necrosis and a serosanguineous pleural effusion. Thrombosis of pulmonary vessels was found in 11 horses.

Clinical Implications—

An acute or peracute onset of severe respiratory distress, with serosanguineous nasal discharge, ultrasonographic and radiographic evidence of severe pulmonary consolidation, and serosanguineous suppurative pleural effusion, is strongly suggestive of pulmonary infarction in horses. Horses with pulmonary infarction responded poorly to conventional treatment for pleuropneumonia and had a poor prognosis for recovery. (J Am Vet Med Assoc 1997;210:1774–1778)

Free access
in Journal of the American Veterinary Medical Association

Objective

To describe clinical manifestations of Corynebacterium pseudotuberculosis infection in horses and to evaluate diagnostic methods for identification of this disease.

Design

Retrospective case series.

Animals

538 horses with a diagnosis of C pseudotuberculosis infection.

Results

Median age of horses with external abscesses was similar to that in horses with internal abscesses. Breed and sex did not appear to be associated with infection. Cases were detected during all 12 months; however, the disease was most common in the fall and early winter, with the highest incidence in September, October, and November in every year. Most horses (492/538, 91.4%) had a single episode of infection, without recurrence in subsequent years. Of 538 horses, 308 had pectoral abscesses, although infection was documented in many other anatomic locations. Forty-two horses had internal abscesses involving the abdomen or thoracic cavity. Corynebacterium pseudotuberculosis infection was readily identified by bacterial culture of aspirate samples from abscesses. The synergistic hemolysis inhibition test was useful for diagnosis of internal abscesses; however, it was unreliable for the diagnosis of external abscesses. Horses with external abscesses responded well to conventional treatment, in contrast to those with internal abscesses. The overall case fatality was low (3.9%), and was considerably lower for horses with external abscesses (0.8%) than for horses with internal abscesses (40.5%).

Clinical Implications

Serology (synergistic hemolysis inhibition titers ≥ 512) is useful for diagnosis of internal abscesses, but not reliable for diagnosis in horses with exernal abscesses. Prognosis for horses with internal abscesses is considerably poorer than for those with external abscesses. (J Am Vet Med Assoc 1996;209:804–809)

Free access
in Journal of the American Veterinary Medical Association