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Abstract

OBJECTIVE

To evaluate physical compatibility of small animal (SAE) and large animal (LAE) injectable formulations of enrofloxacin with select IV fluids and drugs.

SAMPLE

162 admixtures containing SAE or LAE with saline (0.9% NaCl) solution, lactated Ringer solution (LRS), Plasma-Lyte A (PLA), 6% hydroxyethylstarch 130/0.4 (HES), metoclopramide, or ampicillin-sulbactam.

PROCEDURES

In the first of 2 simultaneously conducted experiments, admixtures containing enrofloxacin (10 mg/kg) and a volume of IV fluid that would be administered over a 20-minute period when dosed at the maintenance infusion rate (40 mL/kg/d for saline solution, LRS, and PLA and 20 mL/kg/d for HES) were created. In the second experiment, enrofloxacin (10 mg/kg) was admixed with saline solution (40 mL/kg/d) and metoclopramide (2 mg/kg/d) or ampicillin-sulbactam (30 mg/kg). In both experiments, admixture components were infused into a flask over 20 minutes assuming patient weights of 5, 10, and 20 kg. Admixtures were created by use of undiluted SAE and SAE diluted 1:1 with saline solution and undiluted LAE and LAE diluted 1:1 and 1:10 with saline solution. Admixtures were assessed for physical incompatibility at 0, 15, 30, and 60 minutes after completion of mixing. Physical incompatibility was defined as gross precipitation, cloudiness, Tyndall effect, or change in turbidity.

RESULTS

Admixtures containing undiluted SAE or LAE were physically incompatible with saline solution, PLA, LRS, and HES. Because saline solution was used to dilute SAE and LAE, all admixtures containing diluted SAE or LAE were also physically incompatible. Physical compatibility of enrofloxacin with metoclopramide or ampicillin-sulbactam could not be assessed because those admixtures also contained saline solution.

CONCLUSIONS AND CLINICAL RELEVANCE

Enrofloxacin was physically incompatible with all tested solutions.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To compare the effect of multiple wound dressings on microbial growth in a perfused equine wound model.

SAMPLE

Abdominal musculocutaneous flaps from 16 equine cadavers.

PROCEDURES

8 full-thickness skin wound covered were created in each flap. Tissues were perfused with saline (0.9% NaCl) solution. Wounds were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (106 CFUs), incubated, and covered with a dressing containing activated charcoal, boric acid, cadexomer iodine, calcium alginate, manuka honey, nanoparticle silver, or polyhexamethylene biguanide or with a control (nonadherent gauze) dressing. Muscle biopsy specimens were obtained at baseline (immediately prior to dressing application) and 6, 12, 18, and 24 hours later for mean bacterial load (MBL) determination. The MBLs at each subsequent time point were compared with that at baseline within dressing types, and MBLs at each time point were compared among dressing types.

RESULTS

MBLs in MRSA-inoculated wounds covered with cadexomer iodine dressings were significantly decreased from baseline at the 6− and 12-hour time points. For P aeruginosa–inoculated wounds, MBLs were significantly increased from baseline in all wounds at various times except for wounds with cadexomer iodine dressings. The MBLs of wounds with cadexomer iodine dressings were lower than all others, although not always significantly different from those for wounds with boric acid, manuka honey, nanoparticle silver, and polyhexamethylene biguanide dressings.

CONCLUSIONS AND CLINICAL RELEVANCE

In this nonviable perfused wound model, growth of MRSA and P aeruginosa was most effectively reduced or inhibited by cadexomer iodine dressings. These results and the effect of the dressings on wound healing should be confirmed with in vivo studies.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the median time to maximum concentration (tmax) of amikacin in the synovial fluid of the tarsocrural joint following IV regional limb perfusion (IVRLP) of the drug in a saphenous vein of horses.

ANIMALS

7 healthy adult horses.

PROCEDURES

With each horse sedated and restrained in a standing position, a 10-cm-wide Esmarch tourniquet was applied to a randomly selected hind limb 10 cm proximal to the point of the tarsus. Amikacin sulfate (2 g diluted with saline [0.9% NaCl] solution to a volume of 60 mL) was instilled in the saphenous vein over 3 minutes with a peristaltic pump. Tarsocrural synovial fluid samples were collected at 5, 10, 15, 20, 25, and 30 minutes after completion of IVRLP. The tourniquet was removed after collection of the last sample. Amikacin concentration was quantified by a fluorescence polarization immunoassay. Median maximum amikacin concentration and tmax were determined.

RESULTS

1 horse was excluded from analysis because an insufficient volume of synovial fluid for evaluation was obtained at multiple times. The median maximum synovial fluid amikacin concentration was 450.5 μg/mL (range, 304.7 to 930.7 μg/mL), and median tmax was 25 minutes (range, 20 to 30 minutes). All horses had synovial fluid amikacin concentrations ≥ 160 μg/mL (therapeutic concentration for common equine pathogens) at 20 minutes after IVRLP.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that, in healthy horses, maintaining the tourniquet for 20 minutes after IVRLP of amikacin in a saphenous vein was sufficient to achieve therapeutic concentrations of amikacin in the tarsocrural joint.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To compare the pharmacokinetics of cefquinome sulfate in ducklings and goslings after IV or IM administration of a single dose.

ANIMALS

216 healthy Muscovy ducklings (Cairina moschata) and 216 healthy Sichuan white goslings (Anser cygnoides).

PROCEDURES

Ducklings and goslings were each randomly assigned to 3 groups (n = 72/group) that received a single dose (2 mg/kg) of injectable cefquinome sulfate administered IV or IM or of injectable cefquinome sulfate suspension administered IM. Blood samples were collected at various points after drug administration (n = 6 birds/time point). Plasma cefquinome concentrations were measured by high-performance liquid chromatography with UV detection, and pharmacokinetic parameters were calculated with a 2-compartment model method.

RESULTS

After IV injection, mean distribution half-life of cefquinome was longer in goslings (0.446 hours) than in ducklings (0.019 hours), whereas volume of distribution at steady state was greater (0.432 vs 0.042 L/kg) and elimination half-life was slower (1.737 vs 0.972 hours). After IM administration of injectable cefquinome sulfate, bioavailability of the drug was higher in goslings (113.9%) than in ducklings (67.5%). After IM administration of injectable cefquinome sulfate suspension, bioavailability was also higher in goslings (123.1%) than in ducklings (96.8%), whereas elimination half-life was slower (6.917 vs 1.895 hours, respectively).

CONCLUSIONS AND CLINICAL RELEVANCE

In goslings, IV administration of cefquinome resulted in slower distribution and metabolism of the drug than in ducklings and IM administration resulted in higher bioavailability. The delayed-release effect of the injectable cefquinome sulfate suspension when administered IM was observed only in goslings.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine plasma pharmacokinetics of metronidazole and imipenem following administration of a single dose PO (metronidazole, 15 mg/kg) or IV (imipenem, 10 mg/kg) in healthy Thoroughbreds and simulate pleural fluid concentrations following multiple dose administration every 8 hours.

ANIMALS

4 healthy Thoroughbreds.

PROCEDURES

Metronidazole and imipenem were administered, and samples of plasma and pleural fluid were collected at predetermined time points. Minimum concentrations of metronidazole and imipenem that inhibited growth of 90% of isolates (MIC90), including 22 clinical Bacteroides isolates from horses with pleuropneumonia, were calculated. For the computer simulation, the target ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC90 for metronidazole was > 70, and the target percentage of time per day that the pleural fluid concentration of imipenem exceeded the MIC90 was > 50%.

RESULTS

Mean ± SD pleural fluid concentrations of metronidazole and imipenem were 12.7 ± 3.3 μg/mL and 12.1 ± 0.9 μg/mL, respectively, 1 hour after administration and 4.9 ± 0.85 μg/mL and 0.3 ± 0.08 μg/mL, respectively, 8 hours after administration. For both antimicrobials, concentrations in the pleural fluid and plasma were similar. The ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC90 for metronidazole was 84.9, and the percentage of time per day the pleural fluid concentration of imipenem exceeded the MIC90 was 70.9%.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that administration of metronidazole (15 mg/kg, PO, q 8 h) or imipenem (10 mg/kg, IV, q 8 h) resulted in their accumulation in the pleural fluid in healthy horses and concentrations were likely to be effective for the treatment of pneumonia and pleuropneumonia caused by Bacteroides spp.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the pharmacokinetics of danofloxacin following IM administration of a single dose (10 mg/kg) in koi (Cyprinus carpio).

ANIMALS

69 healthy adult koi housed in a 980-L flow-through-system tank.

PROCEDURES

3 fish were kept as untreated controls, and the remaining 66 fish were assigned to 11 treatment groups with 6 fish/group. Fish in the treatment groups were given a single dose of danofloxacin (10 mg/kg) IM in the left epaxial musculature. Fifteen, 30, and 45 minutes and 1, 4, 12, 24, 72, 96, 120, and 144 hours after administration of danofloxacin, fish in each treatment group were euthanized, and blood samples and samples of liver, spleen, gill, anterior kidney, posterior kidney, skin and muscle, and scales were collected. Plasma and tissue drug concentrations were determined by liquid chromatography–tandem mass spectrometry, and noncompartmental pharmacokinetic analyses were performed. Tissues from the untreated control fish and fish euthanized 144 hours after danofloxacin administration were examined histologically.

RESULTS

Maximum plasma concentration (mean, 8,315.7 ng/mL) was reached approximately 45 minutes after danofloxacin administration; plasma elimination half-life was 15 hours. Danofloxacin was detected in all examined tissues from all 6 fish euthanized 15 minutes after drug administration and was detected in some tissues from 3 of the 6 fish euthanized 144 hours after drug administration. For all tissues, results of histologic examination were unremarkable.

CONCLUSIONS AND CLINICAL RELEVANCE

IM administration of a single dose (10 mg/kg) of danofloxacin in koi resulted in rapid absorption, with maximum plasma concentration reached approximately 45 minutes after drug administration; the drug could still be detected in some tissues 144 hours after administration.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To evaluate the efficacy of tulathromycin for prevention of abortion in pregnant ewes when administered within 24 hours after experimental inoculation with Campylobacter jejuni.

ANIMALS

20 pregnant ewes between 72 and 92 days of gestation.

PROCEDURES

All ewes were inoculated with a field strain of C jejuni (8.5 × 108 to 10.6 × 108 CFUs, IV). Eighteen hours later, ewes received either tulathromycin (1.1 mL/45 kg [2.4 mg/kg], SC; n = 10) or sterile saline (0.9% NaCl) solution (1.1 mL/45 kg, SC; sham; 10). Ewes were euthanized immediately after observation of vaginal bleeding, abortion, or completion of a 21-day observation period. Necropsy was performed on all ewes, and tissue specimens were obtained for bacterial culture and histologic examination.

RESULTS

1 sham-treated ewe and 1 tulathromycin-treated ewe developed signs of severe endotoxemia and were euthanized within 24 hours after C jejuni inoculation. Seven sham-treated and 2 tulathromycin-treated ewes developed vaginal bleeding or aborted and were euthanized between 4 and 21 days after C jejuni inoculation. The proportion of tulathromycin-treated ewes that developed vaginal bleeding or aborted during the 21 days after C jejuni inoculation (2/9) was significantly less than that for the sham-treated ewes (7/9).

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that administration of tulathromycin to pregnant ewes following exposure to C jejuni was effective in decreasing the number of C jejuni–induced abortions. Because of concerns regarding the development of macrolide resistance among Campylobacter strains, prophylactic use of tulathromycin in sheep is not recommended.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To characterize antimicrobial prescribing patterns of clinicians and clinical services at a large animal veterinary teaching hospital and identify factors associated with antimicrobial prescribing.

ANIMALS

All large animals (ie, equids, bovids, sheep, goats, camelids, swine, and cervids) evaluated at the New Bolton Center hospital at the University of Pennsylvania from 2013 through 2018.

PROCEDURES

In a cross-sectional study design, data on antimicrobial use by clinicians and clinical services were collected from administrative and billing records. Multivariable regression modeling was performed to identify factors associated with antimicrobial prescribing patterns.

RESULTS

Antimicrobials and critically important antimicrobials of the highest priority were dispensed in 42.1% (9,853/23,428) and 24.0% (2,360/9,853) of visits, respectively, and these proportions differed significantly among clinicians. Per visit, the median (interquartile [25th to 75th percentile] range) number of animal-defined daily doses dispensed was 3.6 (0.8 to 11.1) and the mean (SD) number of antimicrobial classes dispensed was 2.0 (1.3). Patient species, age, affected body system, and duration of hospitalization as well as submission of specimens for bacterial culture were significantly associated with prescribing patterns.

CONCLUSIONS AND CLINICAL RELEVANCE

The frequency and quantity of antimicrobials prescribed differed significantly among clinicians within and across services, even for animals with clinical signs affecting the same body system. Patient- and visit-level factors explained some but not all of the heterogeneity in prescribing patterns, suggesting that other clinician-specific factors drove such practices. More research is needed to better understand antimicrobial prescribing patterns of clinicians, particularly in situations for which no antimicrobial use guidelines have been established.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine whether therapeutic concentrations (> 0.5 to 1.0 μg/mL) of polymyxin B (PB) were achieved in the tarsocrural joint of horses when the drug was administered by IV regional limb perfusion (IV-RLP) via a saphenous vein at doses of 25, 50, and 300 mg and to describe any adverse systemic or local effects associated with such administration.

ANIMALS

9 healthy adult horses.

PROCEDURES

In the first of 2 experiments, 6 horses each received 25 and 50 mg of PB by IV-RLP via a saphenous vein with at least 2 weeks between treatments. For each treatment, a tourniquet was placed at the midmetatarsus and another was placed midway between the stifle joint and tarsus. Both tourniquets were removed 30 minutes after the assigned dose was administered. Blood and tarsocrural joint fluid samples were collected for determination of PB concentration before and at predetermined times after drug administration. In experiment 2, 4 horses were administered 300 mg of PB by IV-RLP in 1 randomly selected pelvic limb in a manner identical to that used in experiment 1.

RESULTS

For all 3 doses, the mean synovial fluid PB concentration was > 10 times the therapeutic concentration and below the level of quantification at 30 and 1,440 minutes after drug administration, respectively. No adverse systemic or local effects were observed following PB administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that IV-RLP of PB might be a viable alternative for treatment of horses with synovial infections caused by gram-negative bacteria.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the pharmacokinetics of enrofloxacin after IV administration in American black vultures (Coragyps atratus), to compare clearance of enrofloxacin in American black vultures with clearance of this fluoroquinolone in other avian species, and to evaluate whether allometric scaling is an appropriate tool for dose extrapolation in avian species.

ANIMALS

6 healthy adult American black vultures.

PROCEDURES

Enrofloxacin concentrations were quantified by use of high-performance liquid chromatography. Pharmacokinetics of enrofloxacin was determined in American black vultures after IV administration. Pharmacokinetic parameters for 12 avian species obtained from 24 pharmacokinetic studies were used. Allometric analysis of enrofloxacin pharmacokinetic parameters was performed.

RESULTS

Volume of distribution at steady state for enrofloxacin was 3.47 L/kg, clearance was 0.147 L/h·kg, and elimination half-life was 18.3 hours. Comparisons among avian species revealed that American black vultures had the lowest extraction ratio for enrofloxacin (1.04%). Only the volume of distribution at steady state and clearance had a good allometric fit. Goodness of fit was improved when ratites were not included in the analysis.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested that the use of allometric scaling for the prediction of volume of distribution at steady state could provide a suitable method for extrapolation of enrofloxacin doses among avian species; however, allometric scaling could not be used to adequately predict the clearance of enrofloxacin.

Restricted access
in American Journal of Veterinary Research