@article{mzyk_halleran_sylvester_giles_jacob_baynes_foster_2024, title={Continuous sampling of healthy and mastitic quarters of lactating cattle by ultrafiltration after intramammary ceftiofur hydrochloride administration}, volume={8}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17155}, DOI={10.1111/jvim.17155}, abstractNote={Abstract Background Pharmacological activity of intramammary drugs depends on adequate drug concentrations within the cistern, but sampling is often limited. Insight into the active drug concentration within the mammary cistern may assist in determining effective and appropriate therapeutic decisions for cows being treated for mastitis. Objective Evaluate the disposition of ceftiofur hydrochloride administered intramammary in diseased and nondiseased quarters. Whole milk and ultrafiltrate sampling techniques were compared. Animals Ten mature, late lactation Holstein (n = 9) and Jersey (n = 1) dairy cows (422‐670 kg) with naturally occurring clinical mastitis, producing between 1.4 and 15.9 kg/day of milk. Methods Ultrafiltration probes were placed in both mastitic and healthy quarters. Each quarter was treated with 2 doses of 125 mg ceftiofur hydrochloride suspension, and whole milk and milk ultrafiltrate samples were collected. Ceftiofur concentrations in composite whole milk and milk ultrafiltrate were analyzed. Results The maximum concentration of ceftiofur was higher in ultrafiltrate samples, but no differences were identified in healthy or mastitic quarters. The use of ultrafiltration probes provides a novel technique for free drug concentrations within the mastitic and healthy bovine mammary gland. Conclusions and Clinical Importance Significant inter‐ and intracow variability and lower daily milk weights may overestimate ceftiofur concentrations available within the cistern. The pharmacokinetic (PK) parameters reported in milk ultrafiltrate will help establish a link between the PK and the corresponding drug effect, potentially providing a meaningful rationale for the selection of a safe and effective dose in cows with mastitis.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Mzyk, Danielle A. and Halleran, Jennifer L. and Sylvester, Hannah J. and Giles, Claire B. and Jacob, Megan E. and Baynes, Ronald E. and Foster, Derek M.}, year={2024}, month={Aug} } @article{giles_ferdous_halleran_yeatts_baynes_mzyk_2024, title={Flunixin meglumine tissue residues after intravenous administration in goats}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1341779}, abstractNote={BackgroundFlunixin is commonly used in goats in an extra-label manner, indicating a significant need to determine withdrawal intervals for edible tissues.ObjectiveThe objectives of the present study were to investigate the depletion of flunixin meglumine in various goat tissues, including the liver, kidney, fat, and muscle.MethodsTwenty Boer goats were enrolled and administered an intravenous dose (2.2 mg/kg) of flunixin meglumine. Five animals were randomly euthanized at 24, 48, 72, or 96 h following dosing. All samples were analyzed via ultra-performance liquid chromatography coupled with mass spectrometry.ResultsThe concentration of flunixin in all tissues declined rapidly, with the highest mean concentrations quantified in the kidney (0.137 ± 0.062 μg/g) and liver (0.077 ± 0.029 μg/g) tissues at 24 h.ConclusionSince any detection of flunixin residues at slaughter found in goat tissues is considered a violative residue, a conservative withdrawal interval of 17 days was calculated to ensure levels of flunixin fell below the regulatory limits of detection in liver, kidney, and muscle tissues.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Giles, Claire B. and Ferdous, Farha and Halleran, Jennifer L. and Yeatts, Jim L. and Baynes, Ronald E. and Mzyk, Danielle A.}, year={2024}, month={Jan} } @article{halleran_sylvester_jacob_callahan_baynes_foster_2024, title={Impact of florfenicol dosing regimen on the phenotypic and genotypic resistance of enteric bacteria in steers}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-55591-8}, abstractNote={AbstractThe food animal sector’s use of antimicrobials is heavily critiqued for its role in allowing resistance to develop against critically important antimicrobials in human health. The WHO recommends using lower tier antimicrobials such as florfenicol for disease treatment. The primary objective of this study was to assess the differences in resistance profiles of enteric microbes following administration of florfenicol to steers using both FDA-approved dosing regimens and two different detection methods. Our hypothesis was that we would identify an increased prevalence of resistance in the steers administered the repeated, lower dose of florfenicol; additionally, we hypothesized resistance profiles would be similar between both detection methods. Twelve steers were administered either two intramuscular (20 mg/kg q 48 h; n = 6) or a single subcutaneous dose (40 mg/kg, n = 6). Fecal samples were collected for 38 days, and E. coli and Enterococcus were isolated and tested for resistance. Fecal samples were submitted for metagenomic sequencing analysis. Metagenomics revealed genes conferring resistance to aminoglycosides as the most abundant drug class. Most multidrug resistance genes contained phenicols. The genotypic and phenotypic patterns of resistance were not similar between drug classes. Observed increases in resistant isolates and relative abundance of resistance genes peaked after drug administration and returned to baseline by the end of the sampling period. The use of a “lower tier” antimicrobial, such as florfenicol, may cause an increased amount of resistance to critically important antimicrobials for a brief period, but these changes largely resolve by the end of the drug withdrawal period.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Halleran, Jennifer and Sylvester, Hannah and Jacob, Megan and Callahan, Benjamin and Baynes, Ronald and Foster, Derek}, year={2024}, month={Feb} } @article{camacho_mitman_foster_halleran_2024, title={Validation of a reference interval for symmetric dimethylarginine in healthy goats and its comparison to values in goats with obstructive urolithiasis}, volume={8}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.17162}, abstractNote={Abstract Background Symmetric dimethylarginine (SDMA), a sensitive biomarker for detecting renal injury, has not been characterized in goats. Obstructive urolithiasis (OU) is the most common urinary tract disease in male small ruminants. Hypothesis/Objective Establish an SDMA reference interval (RI) in healthy adult goats and describe SDMA concentrations in goats with OU. We hypothesize that the SDMA RI in healthy adult goats will be similar to that of other adult veterinary species and that SDMA can be utilized to assess the renal function of goats experiencing OU. Animals Fifty‐five healthy adult male and female goats from a university herd were enrolled for SDMA RI development. Twenty male and female goats from a university herd were enrolled for validation of the SDMA RI established. Thirteen male goats diagnosed with OU were enrolled. Methods Clinical trial. Serum samples for all animals enrolled were collected and analyzed for SDMA using an immunoassay (IDEXX Laboratories, Inc); goats with OU had additional blood work analyzed (PCV, total solids, and serum biochemistry). Symmetric dimethylarginine and other values in goats with OU were analyzed and compared at specific time points. Results The SDMA RI for healthy, adult goats is 8.03 μg/dL (90% CI 4.81‐11.04) to 25.93 μg/dL (90% CI 22.88‐28.97). There was no correlation identified between serum creatinine and SDMA in goats with OU. Conclusions and Clinical Importance The SDMA RI for adult goats is higher than in other adult large animal species. Use of SDMA in goats with OU is not useful in assessing their renal function.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Camacho, Blanca E. and Mitman, Siena L. and Foster, Derek M. and Halleran, Jennifer}, year={2024}, month={Aug} } @article{halleran_minch_slyvester_jacob_prange_baynes_foster_2021, title={Comparison of the Intestinal Pharmacokinetics of Two Different Florfenicol Dosing Regimens and Its Impact on the Prevalence and Phenotypic Resistance of E. coli and Enterococcus over Time}, volume={9}, ISSN={["2076-2607"]}, DOI={10.3390/microorganisms9091835}, abstractNote={In order to mitigate the food animal sector’s role in the growing threat of antimicrobial resistance (AMR), the World Health Organization (WHO) suggests the use of lower tier antimicrobials, such as florfenicol. Florfenicol has two dosing schemes used to treat primarily bovine respiratory disease. In this study, the objective was to characterize the plasma and gastrointestinal pharmacokinetics of each dosing regimen and assess the effect of these dosing regimens on the prevalence of resistant indicator bacteria over time. Twelve steers underwent abdominal surgery to facilitate the placement of ultrafiltration probes within the lumen of the ileum and colon, as well as placement of an interstitial probe. Following surgery, cattle were dosed with either 20 mg/kg IM every 48 h of florfenicol given twice (n = 6) or a single, subcutaneous dose (40 mg/kg, n = 6). Plasma, interstitial fluid, gastrointestinal ultrafiltrate, and feces were collected. Pharmacokinetic analysis demonstrated high penetration of florfenicol within the gastrointestinal tract for both the high and low dose group (300%, 97%, respectively). There was no significant difference noted between dosing groups in proportion or persistence of phenotypically resistant bacterial isolates; however, the percent of resistant isolates was high throughout the study period. The recommendation for the use of a lower tier antimicrobial, such as florfenicol, may allow for the persistence of co-resistance for antibiotics of high regulatory concern.}, number={9}, journal={MICROORGANISMS}, author={Halleran, Jennifer L. and Minch, Ryker and Slyvester, Hannah J. and Jacob, Megan E. and Prange, Timo and Baynes, Ronald and Foster, Derek M.}, year={2021}, month={Sep} } @article{halleran_callahan_jacob_sylvester_prange_papich_foster_2021, title={Effects of danofloxacin dosing regimen on gastrointestinal pharmacokinetics and fecal microbiome in steers}, volume={11}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-021-90647-z}, abstractNote={AbstractFluoroquinolones are a class of antimicrobial commonly used in human medicine, and deemed critical by the World Health Organization. Nonetheless, two formulations are approved for the treatment of respiratory disease in beef cattle. The objective of this study was to determine the gastrointestinal pharmacokinetics and impact on enteric bacteria of cattle when receiving one of the two dosing regimens (high: 40 mg/kg SC once or low: 20 mg/kg IM q48hr) of danofloxacin, a commonly utilized synthetic fluoroquinolone in veterinary medicine. Danofloxacin was administered to 12 steers (age 7 months) fitted with intestinal ultrafiltration devices at two different dosing regimens to assess the gastrointestinal pharmacokinetics, the shifts in the gastrointestinal microbiome and the development of resistant bacterial isolates. Our results demonstrated high intestinal penetration of danofloxacin for both dosing groups, as well as, significant differences in MIC values for E. coli and Enterococcus between dosing groups at selected time points over a 38 day period. Danofloxacin treatment consistently resulted in the Euryarchaeota phyla decreasing over time, specifically due to a decrease in Methanobrevibacter. Although microbiome differences were minor between dosing groups, the low dose group had a higher number of isolates with MIC values high enough to cause clinically relevant resistance. This information would help guide veterinarians as to appropriate dosing schemes to minimize the spread of antimicrobial resistance.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Halleran, J. L. and Callahan, B. J. and Jacob, M. E. and Sylvester, H. J. and Prange, T. and Papich, M. G. and Foster, D. M.}, year={2021}, month={May} } @article{halleran_yau_paegelow_streeter_foster_2021, title={Mycobacterial Cell Wall Stimulant in the Treatment of Squamous Cell Carcinoma: A Case Series Regarding Treatment in Equine, Bovine and Caprine Patients}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.635800}, abstractNote={Squamous cell carcinoma (SCC) is a common dermatological neoplasia found in large animal species. Treatment options, such as surgery and cryotherapy may be difficult or not feasible. Alternative therapies, such as immunomodulating drugs, can potentially be used for companion large animals. The hypothesis of the following retrospective study is: following multiple intravenous and intralesional injections of a mycobacterial cell wall stimulant (MCW) regression of SCC in equine, bovine and caprine patients will be observed. In this observational-retrospective case series, patients included are 2 bovine, 2 caprine and 3 equine patients. The medical records at two different teaching veterinary hospitals were searched for cases with a positive histopathological diagnosis of squamous cell carcinoma that were subsequently treated with MCW, as either the sole therapy, or in conjunction with other therapies. Seven cases were included in this retrospective study. The median duration of therapy was 56.5 days, with 3 of the 7 patients being euthanized. Significant complications were seen in 3/7 patients. Repeated injections of a MCW may lead to reduction in lesion size of SCC in some cases, but long-term resolution is unlikely and the risk of significant complications is high; due to limited sample size and the variety in species, it is difficult to conclude if MCW is an effective therapy for SCC.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Halleran, Jennifer and Yau, Katie and Paegelow, Jillian and Streeter, Robert and Foster, Derek}, year={2021}, month={Aug} } @article{yau_halleran_boileau_foster_2021, title={Retrospective study on the use of lidocaine constant rate infusions for the treatment of ileus in ruminants and camelids}, volume={9}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16262}, abstractNote={AbstractLimited knowledge exists regarding the use of lidocaine as a prokinetic in ruminants and camelids to treat gastrointestinal ileus. In this retrospective study, ruminant and camelid cases diagnosed with ileus and treated with a lidocaine constant rate of infusion were assessed for adverse reactions and medical outcomes. A review of medical records was performed to identify cases in which lidocaine was administered as a prokinetic. Ten cases were identified consisting of 8 cattle, 1 goat, and 1 alpaca. Nine animals improved with a lidocaine treatment. No adverse effects were reported during lidocaine administration. Nine animals were discharged, and 1 was euthanized.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Yau, Katie and Halleran, Jennifer and Boileau, Melanie and Foster, Derek}, year={2021}, month={Sep} } @article{halleran_papich_li_lin_davis_maunsell_riviere_baynes_foster_2022, title={Update on withdrawal intervals following extralabel use of procaine penicillin G in cattle and swine}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.21.05.0268}, abstractNote={IntroductionExtralabel drug use (ELDU) is defined as the use of an FDA-approved medication in a manner that differs from what is provided on the label of the medication.1 Administration of the medication to a different species or at a different dose, volume, route, duration, indication, or frequency than indicated on the label is considered ELDU. Extralabel drug use also requires an extended withdrawal period to avoid violative residues, and practitioners can get advice on withdrawal intervals (WDIs) following ELDU from the Food Animal Residue Avoidance and Depletion Program (FARAD). Penicillin is one of the most commonly used}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Halleran, J.L. and Papich, M.G. and Li, M. and Lin, Z. and Davis, J. and Maunsell, F. and Riviere, J. and Baynes, R. and Foster, D.M.}, year={2022}, month={Jan}, pages={50–55} }