Objective—To determine disposition kinetics of
amikacin in neonatal foals administered high doses at
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)
Objective—To determine pharmacokinetics and plasma
concentrations of erythromycin and related compounds
after intragastric administration of erythromycin
phosphate and erythromycin estolate to
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)
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)
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
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:
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
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)