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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

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)

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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)

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in American Journal of Veterinary Research

Abstract

Objective—To characterize isolates of Corynebacterium pseudotuberculosis from horses, cattle, and sheep in Colorado, Kentucky, Utah, and California in samples collected during perceived epidemics of infection (increased numbers of cases identified) in 2002 and 2003, and determine how closely isolates were related and their possible source.

Sample Population—54 isolates of C pseudotuberculosis from 49 horses, 4 cattle, and 1 sheep.

Procedures—Random amplified polymorphic DNA (RAPD) polymerase chain reaction (PCR) assay, PCR assay for the gene encoding the phospholipase D (PLD) toxin, biochemical analyses, and tests for susceptibility to 17 antimicrobial drugs were performed.

Results—All isolates reduced nitrate to nitrite, most yielded positive results for the PLD toxin gene, and all were susceptible to antimicrobial drugs. Ten genetic types were detected by use of RAPD PCR assay; types III to X were isolated from horses, cattle, or both in 1 or more states. Types III and IX were isolated from both horses and cattle. Types VII and VIII were isolated in only 1 state, but the number of isolates in these groups was small. In contrast, all other types were isolated in 2 or more states. All isolates from Utah were type III, but the other 3 states had isolates from more than 1 type.

Conclusions and Clinical Relevance—These data are consistent with a clonally expanding epidemic of infection in Utah and an increase in number of infections caused by multiple strains of C pseudotuberculosis not derived from a single source in the other states. The increase in number of infections could be the result of reporting bias, environmental factors facilitating infection, or host factors such as greater herd susceptibility. (Am J Vet Res 2004;65:1734–1737)

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in American Journal of Veterinary Research

Abstract

Objective

To determine whether oral administration of erythromycin alters the inflammatory response to bronchoalveolar lavage (BAL) in young horses.

Animals

12 healthy, unweaned, mixed-breed foals of either sex, between 2 and 4 months old.

Procedure

BAL was performed; 250 ml of phosphate-buffered saline solution (300 mOsm, pH 7.4) was administered in 50-ml aliquots. Foals were carefully monitored for 4 days, then erythromycin base (25 mg/kg of body weight, PO, q 12 h) was given to foals of the treated group. After 4 days, foals were re-anesthetized, and the same lung was relavaged. Cytologic examination was performed on BAL fluid (BALF) samples from both groups of foals. At 12 hours after administration of the final dose, erythromycin A and anhydroerythromycin A concentrations were determined in plasma of treated foals.

Results

In the second BALF sample from the same lung of control foals, percentage of neutrophils was significantly increased (3 ± 38.0%), compared with that from erythromycin-treated foals (4.88 ± 3.66%, P < 0.05), and was associated with apparent decrease in the ability of BALF cells from erythromycin-treated foals to migrate toward a chemoattractant source. Significantly fewer BALF cells adhered to a cell culture substratum after erythromycin treatment of foals. Erythromycin A was not detected in plasma of any treated foal at the time of the second BAL; anhydroerythromycin A, a degradation product of erythromycin, was detected in plasma of 5 of 6 foals (mean concentration, 0.2 ± 0.06 µg/ml).

Conclusion and Clinical Relevance

BAL induces neutrophilic inflammation, which persists for at least 4 days in the lungs of young horses. Erythromycni (25 mg/kg, PO, q 12 h) diminishes this inflammatory response through a mechanism that may involve alteration of BALF cell function. Degradation of erythromycin to biologically active products or presence of parent drug in pulmonary secretions may be responsible for alterations in pulmonary lavage cell Chemotaxis and adherence. Erythromycin administered orally to foals at clinically relevant doses appears to have nonantimicrobial effects that may interfere with host cell metabolism and decrease inflammatory reponses in airways. (Am J Vet Res 1997;58:56–61)

Free access
in American Journal of Veterinary Research

SUMMARY

The effect of age on the pharmacokinetics of chloramphenicol was determined after iv administration of chloramphenicol sodium succinate (25 mg/kg of body weight) to 6 foals at 1 day and 3, 7, 14, and 42 days of age. The disposition of chloramphenicol was best described, using a two-compartment open model in all foals at all ages evaluated. Significant age-related changes were observed in values for the major kinetic terms describing the disposition of chloramphenicol in foals; the greatest changes were observed between 1 day and 3 days of age.

The mean ± sd value for elimination rate constant (β) for chloramphenicol in 1-day-old foals (0.131 ± 0.06 h-1) was significantly (P < 0.005) lower than the value in 3-day-old foals (0.514 ± 0.156 h-1), and both values were significantly (P < 0.05) lower than values for β in 7-, 14-, and 42-day-old foals. With increasing age, the increase in the mean value for β resulted in decrease in the harmonic mean elimination half-time (t1/2β) for chloramphenicol, from 5.29 hours in 1-day-old foals to: 1.35 hours in 3-day-old foals; 0.61 hour in 7-day-old foals; 0.51 hour in 14-day-old foals; and 0.34 hour in 42-day-old foals. At 1, 3, and 7 days of age, values for t1/2β of chloramphenicol in a premature foal born after parturition was induced with oxytocin, were considerably longer than comparable t1/2β values for term foals born naturally.

The mean body clearance (ClB) of chloramphenicol in 1-day-old foals (2.25 ± 0.67 ml/min·kg of body weight) was significantly lower than values in: 3-day-old (6.23 ± 2.22 ml/min·kg; P < 0.05); 7-day-old (8.86 ± 1.90 ml/min·kg; P < 0.0005); 14-day-old (9.63 · 1.63 ml/min·kg; P < 0.0005); and 42-day-old (9.68 · 2.76 ml/min·kg; P < 0.0001) foals. In foals of all ages, ClB of chloramphenicol in the parturition-induced premature foal was lower than the mean value for term foals born naturally.

The volume of distribution (V′d[area]) of chloramphenicol decreased progressively with increasing age between day 1 and day 42, so that the mean value for 42-day-old foals (362 ± 163 ml/kg) was less than a third the mean value for 1-day-old foals (1,101 ± 284 ml/kg). The mean value for V′d(area) in 1-day-old foals was significantly greater than values for: 7-day-old (491 ± 158 ml/kg; P < 0.01); 14-day-old (426 ± 65 ml/kg; P < 0.005); and 42-day-old (362 ± 162; P < 0.0005) foals, and the mean value for V′d(area)on day 3 was significantly (P < 0.05) greater than the mean value for V′d(area) on days 7, 14, and 42.

Using dosage calculations based on mean values for the pharmacokinetic terms derived for each age group, it was predicted that to maintain plasma chloramphenicol concentration > 8 μg/ml, chloramphenicol sodium succinate (25 mg/kg) would have to be administered at dose intervals of 10, 3, 1.5, 1.5, and 1 hours in clinically normal foals 1 day and 3, 7, 14, and 42 days, of age, respectively. It was concluded that the marked changes in the disposition of chloramphenicol detectable during the first few days of life, the variation between individuals, the potentially major effect of prematurity, and the potential for compromised liver function in septicemic foals indicate that use of drugs, such as chloramphenicol, which rely heavily on hepatic metabolic processes for elimination, should be avoided whenever possible during the early neonatal period, unless plasma concentration is monitored.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To develop and use a sensitive molecular assay for detecting the phospholipase D (PLD) exotoxin gene of Corynebacterium pseudotuberculosis in an attempt to identify insect vectors that may be important in transmission of clinical disease in horses.

Sample Population—2,621 flies of various species.

Procedure—A real-time polymerase chain reaction (PCR)-based fluorogenic 5' nuclease (TaqMan) system (ie, TaqMan PCR assay) was developed for the detection of the PLD gene in insects. Flies were collected monthly (May to November 2002) from 5 farms in northern California where C pseudotuberculosis infection in horses is endemic. Three of the 5 farms (which housed a total of 358 horses) had diseased horses during the study period. A total of 2,621 flies of various species were tested for the PLD gene of C pseudotuberculosis.

Results—Evidence of bacterial DNA for the PLD gene was detected in skin biopsy specimens from clinically affected horses and from 3 fly species collected from farms where affected horses were housed. Farms with a high incidence of diseased horses had a high proportion of insects carrying the organism. High percentages of flies with positive results for the PLD gene were observed in October, when most clinically affected horses were observed.

Conclusions and Clinical Relevance—Our results are consistent with the hypothesis that C pseudotuberculosis may be vectored to horses by flies. Three potential vectors were identified, including Haematobia irritans, Stomoxys calcitrans, and Musca domestica. The organism can be identified in up to 20% of house flies (Musca domestica) in the vicinity of diseased horses. (Am J Vet Res 2004;65:829–834)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the efficacy of florfenicol for treatment of calves with naturally occurring infectious bovine keratoconjunctivitis (IBK).

Design—Randomized controlled field trial.

Animals—63 beef calves and 80 dairy calves between 4 and 12 months of age.

Procedure—Calves were randomly assigned to 1 of 3 treatment groups. Calves in the SC treatment group received a single dose of florfenicol (40 mg/kg [18.2 mg/lb] of body weight), SC, on day 0. Calves in the IM treatment group received florfenicol (20 mg/kg [9.1 mg/lb]), IM, on days 0 and 2. Calves in the control group received injections of saline solution (0.9% NaCl), IM, on days 0 and 2. Calves were reevaluated every other day for 20 days after treatment.

Results—Corneal ulcers healed by day 20 in 48 of 49 (98%) calves treated with florfenicol IM, 39 of 42 (93%) calves treated with florfenicol SC, and 33 of 52 (63%) control calves.

Conclusions and Clinical Relevance—Florfenicol administered SC (1 dose) or IM (2 doses 48 hours apart) was effective for treatment of calves with naturally occurring IBK. ( J Am Vet Med Assoc 2000;216: 62–64)

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in Journal of the American Veterinary Medical Association