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Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As

Corynebacterium pseudotuberculosis causes chronic, suppurative, abscessing conditions in livestock and humans. We used an in vivo model to evaluate antimicrobial efficacy for focal abscesses caused by C. pseudotuberculosis. Tissue chambers were surgically implanted in the subcutaneous tissues of the right and left paralumbar fossa of 12 goats to serve as a model for isolated, focal abscesses. For each goat, one tissue chamber was inoculated with C. pseudotuberculosis, while the contralateral chamber served as an uninoculated control. Six goats were administered a single dose of tulathromycin at 2.5 mg/kg of body weight subcutaneously, while the other six received the same dose by injection directly into the inoculated chambers. Our objective was to compare the effects and tulathromycin concentrations in interstitial fluid (IF) samples collected from C. pseudotuberculosis-infected and control chambers following subcutaneous or intrachamber injection of tulathromycin. In addition, the effects of tulathromycin on the quantity of C. pseudotuberculosis reisolated from inoculated chambers were assessed over time. Tulathromycin IF concentrations from C. pseudotuberculosis-infected and control tissue chambers were similar to those in plasma following subcutaneous administration. Following intrachamber administration, tulathromycin IF concentrations in infected chambers were continuously above the MIC for the C. pseudotuberculosis isolate for 15 days. There were no significant differences for plasma area under the curve and elimination half-lives between subcutaneous and intrachamber administration. Six of the 12 infected chambers had no growth of C. pseudotuberculosis 15 days postadministration. Results of this study indicate that tulathromycin may be beneficial in the treatment of focal infections such as those caused by C. pseudotuberculosis.

Antibiograms are important tools for antimicrobial stewardship that are often underutilized in veterinary medicine. Antibiograms summarize cumulative antimicrobial susceptibility testing (AST) data for specific pathogens over a defined time period; in veterinary medicine, they are often stratified by host species and site of infection. They can aid practitioners with empiric therapy choices and assessment of antimicrobial resistance trends within a population in support of one-health goals for antimicrobial stewardship. For optimal application, consideration must be given to the number of isolates used, the timeframe of sample collection, laboratory analytical methodology, and the patient population contributing to the data (eg, treatment history, geographic region, and production type). There are several limitations to veterinary antibiograms, including a lack of breakpoint availability for bacterial species, a lack of standardization of laboratory methodology and technology for culture and AST, and a lack of funding to staff veterinary diagnostic laboratories at a level that supports antibiogram development and education. It is vital that veterinarians who use antibiograms understand how to apply them in practice and receive relevant information pertaining to the data to utilize the most appropriate antibiogram for their patients. This paper explores the benefits and challenges of developing and using veterinary antibiograms and proposes strategies to enhance their applicability and accuracy. Further detail regarding the application of veterinary antibiograms by privately practicing clinicians is addressed in the companion Currents in One Health article by Lorenz et al (JAVMA, September 2023).

Antimicrobial susceptibility testing (AST) is an important component of antimicrobial stewardship. This article discusses how AST methods and breakpoints are developed, describes when AST may or may not be useful in clinical practice, and discusses how to interpret AST results from bacterial isolates from cattle, sheep, and goats. Discussion of when AST is not appropriate or when veterinarians should have low confidence in AST results is also included. Applicability of genomic testing for antimicrobial susceptibility is briefly addressed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Veterinarians contribute substantially to the health of their patients and enhance the communities in which they live. Delivery of veterinary curricula continues to evolve to ensure that veterinary graduates are prepared to meet their professional obligations on Day One of their careers. In this study, veterinary practitioners were recruited to deliver telehealth case rounds to veterinary students at Kansas State University and Texas A&M University. Case discussions were hosted virtually once per month in the 2020-2021 and 2021-2022 academic years for a total of 16 sessions. Each presenting practitioner was instructed to develop a brief presentation for a case routinely seen in their practice, and to discuss important clinical decision points in diagnosis, treatment and management. Cases could also highlight important ethical or communication issues encountered in veterinary medicine. The overall goals of this project were to increase the quantity and diversity of clinical cases to which veterinary students were exposed during their professional training and to evaluate the feasibility and acceptability of telehealth technology as a teaching strategy. Student participants were surveyed to determine the effectiveness of telehealth sessions in increasing overall confidence and competence in case management, and veterinary presenters were surveyed to determine motivations for participating in the project and perceived value of the telehealth sessions. More than 95% of students indicated that participation in telehealth sessions increased their clinical confidence and competence. Presenting practitioners unanimously indicated that they would participate in similar instruction in the future. Recommendations are provided to improve the educational experience for future adopters of telehealth teaching sessions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lubbers, Fajt, Teller, Apley and Stillisano.)

The objective of this study was to determine the pharmacokinetics of firocoxib after oral administration in un-weaned calves. Eight Holstein calves with a mean age of 36 days and a mean weight of 55 kg were administered a single oral dose of 227 mg firocoxib. The resulting mean dosage was 4.2 mg/kg (range 3.5-5.0 mg/kg). Blood was collected prior to drug administration and at 2, 4, 6, 8, 24, 48, 72, and 96 h after treatment. Firocoxib concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Using computer software, pharmacokinetic parameters were found to fit best with a one-compartment model. Mean C max was 0.9 μg/ml (range 0.570-1.254), and T max was estimated to be 7 h (range 4-8 h). The estimated T 1/2 was 15.3 h. The pharmacokinetics of firocoxib after oral dosing are similar to those in dogs, with the exception of a T 1/2 that is approximately twice as long. Based on the similar pharmacokinetics, it is possible that a dose of 227 mg firocoxib orally could provide an analgesic effect in un-weaned calves., (© 2021 John Wiley & Sons Ltd.)

Cephalosporin antimicrobials can be utilized for the treatment of sepsis in neonatal foals, particularly when an aminoglycoside is contraindicated. Some cephalosporins, however, are not utilized because of cost, sporadic availability, or uncertainty about efficacy. The plasma disposition of ceftazidime, a third-generation cephalosporin with a broad spectrum of activity against a wide variety of gram-negative bacteria and minimal renal side effects has not been reported in neonatal foals. In this study, the plasma disposition of single intravenous (IV) and intramuscular (IM) doses of ceftazidime in neonatal foals was determined. Six healthy one to two-day-old foals were given 25 mg/kg of ceftazidime by IV and IM routes in a cross-over design, with a 48-h washout period between doses. Non-compartmental analysis was used to estimate plasma pharmacokinetic parameters. Median t 1/2 was 2 h and median AUC 0-last was 364 µg h/ml for both IV and IM administration. Median C max after IM administration was 101 µg/ml, with a median T max of 0.7 h. Relative bioavailability of IM injection was 90%. There were no statistically significant differences between estimated IV and IM pharmacokinetic parameters. Plasma concentrations remained above the human CLSI susceptible breakpoint for Enterobacteriaceae for over 8 h following IV and IM administration., (© 2021 John Wiley & Sons Ltd.)

Background: Combatting antimicrobial resistance requires a One Health approach to antimicrobial stewardship including antimicrobial drug (AMD) use evaluation. Current veterinary AMD prescribing data are limited., Objectives: To quantify companion animal AMD prescribing in primary care and specialty practice across 3 academic veterinary hospitals with particular focus on third-generation cephalosporins, fluoroquinolones, and carbapenems., Animals: Dogs and cats presented to 3 academic veterinary hospitals from 2012 to 2017., Methods: In this retrospective study, AMD prescribing data from 2012 to 2017 were extracted from electronic medical records at each hospital and prescriptions classified by service type: primary care, specialty practice or Emergency/Critical Care (ECC). Hospital-level AMD prescribing data were summarized by species, service type, AMD class, and drug. Multivariable logistic full-factorial regression models were used to estimate hospital, year, species, and service-type effects on AMD prescribing. Estimated marginal means and confidence intervals were plotted over time., Results: The probability of systemic AMD prescribing for any indication ranged between 0.15 and 0.28 and was higher for dogs than cats (P < .05) apart from 2017 at hospital 1. Animals presented to primary care were least likely to receive AMDs (dogs 0.03-0.15, cats 0.03-0.18). The most commonly prescribed AMD classes were aminopenicillins/β-lactamase inhibitors (0.02-0.15), first-generation cephalosporins (0.00-0.09), fluoroquinolones (0.00-0.04), nitroimidazoles (0.01-0.06), and tetracyclines (0.00-0.03). Among the highest priority classes, fluoroquinolones (dogs 0.00-0.09, cats 0.00-0.08) and third-generation cephalosporins (dogs 0.00-0.04, cats 0.00-0.05) were most frequently prescribed., Conclusions and Clinical Importance: Antimicrobial drug prescribing frequencies were comparable to previous studies. Additional stewardship efforts might focus on fluoroquinolones and third-generation cephalosporins., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Though carbapenems are not licensed for use in food animals in the U.S., carbapenem resistance among Enterobacteriaceae has been identified in farm animals and their environments. The objective of our study was to determine the extent to which older-generation β-lactam antibiotics approved for use in food animals in the U.S. might differentially select for resistance to antibiotics of critical importance to human health, such as carbapenems. Escherichia coli (E. coli) strains from humans, food animals, or the environment bearing a single β-lactamase gene (n = 20 each) for blaTEM-1, blaCMY-2, and blaCTX-M-* or else blaKPC/IMP/NDM (due to limited availability, often in combination with other bla genes), were identified, along with 20 E. coli strains lacking any known beta-lactamase genes. Baseline estimates of intrinsic bacterial fitness were derived from the population growth curves. Effects of ampicillin (32 μg/mL), ceftriaxone (4 μg/mL) and meropenem (4 μg/mL) on each strain and resistance-group also were assessed. Further, in vitro batch cultures were prepared by mixing equal concentrations of 10 representative E. coli strains (two from each resistance gene group), and each mixture was incubated at 37°C for 24 hours in non-antibiotic cation-adjusted Mueller-Hinton II (CAMH-2) broth, ampicillin + CAMH-2 broth (at 2, 4, 8, 16, and 32 μg/mL) and ceftiofur + CAMH-2 broth (at 0.5, 1, 2, 4, and 8μg/mL). Relative and absolute abundance of resistance-groups were estimated phenotypically. Line plots of the raw data were generated, and non-linear Gompertz models and multilevel mixed-effect linear regression models were fitted to the data. The observed strain growth rate distributions were significantly different across the groups. AmpC strains (i.e., blaCMY-2) had distinctly less robust (p < 0.05) growth in ceftriaxone (4 μg/mL) compared to extended-spectrum beta-lactamase (ESBL) producers harboring blaCTX-M-*variants. With increasing beta-lactam antibiotic concentrations, relative proportions of ESBLs and CREs were over-represented in the mixed bacterial communities; importantly, this was more pronounced with ceftiofur than with ampicillin. These results indicate that aminopenicillins and extended-spectrum cephalosporins would be expected to propagate carbapenemase-producing Enterobacteriaceae in food animals if and when Enterobacteriaceae from human health care settings enter the food animal environment., Competing Interests: The authors have declared that no competing interests exist.

Background: The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues., Results: Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 µg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 µg/g). Meloxicam was detected in a single liver sample (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g)., Conclusions: These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.

Pain management in rabbits can be difficult because they are adept at hiding pain and can be stressed by handling and restraint for injection. The use of opioid analgesics with prolonged durations of activity could alleviate pain, but associated adverse effects including gastrointestinal ileus, inappetence, and tissue reactions have been reported. In this study, we compared gross tissue reactions at the site of injection, food consumption, and fecal production after single injections of buprenorphine HCl (Bup; n = 7), sustained-release buprenorphine (BupSR; n = 8), and high-concentration buprenorphine (BupHC; n = 7) during the first 3 d after minor survival surgery. We also measured plasma concentrations of the parent drug, buprenorphine, and 3 metabolites (buprenorphine-3-glucuronide (B3G), norbuprenorphine-3β-glucuronide (N3G), and norbuprenorphine (NB)). Plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for 4 h for Bup and 42 h for BupHC. For BupSR, plasma levels of buprenorphine remained above the theoretical minimal analgesic concentration for approximately 77 h, starting 15 h after administration. For all 3 formulations, N3G was the most prominent metabolite in the blood. No injection site reactions were visible grossly in any rabbit. Relative to baseline measures and compared with controls ( n = 8), food consumption was suppressed on days 1 through 3 in rabbits that received BupSR and on days 2 through 3 in those given BupHC. Feces production on day 3 was reduced to a greater extent in BupSR rabbits than control animals. Two rabbits in the BupHC group exhibited neurologic signs after drug administration. These adverse effects should be considered when choosing a long-lasting buprenorphine formulation to manage pain in rabbits.

Objective: To compare analgesic efficacy and fetal effects between transdermal administration of fentanyl and IM administration of buprenorphine in pregnant sheep., Animals: 12 healthy pregnant ewes., Procedures: Before study initiation, each ewe was confirmed pregnant with a single fetus between 113 and 117 days of gestation. Ewes were randomly assigned to receive buprenorphine (0.01 mg/kg, IM, q 8 h for 48 hours beginning 1 hour before anesthesia induction; n = 6) or fentanyl (a combination of transdermal fentanyl patches sufficient to deliver a dose of 2 μg of fentanyl/kg/h applied between the dorsal borders of the scapulae 24 hours before anesthesia induction; 6). Ewes were anesthetized and underwent a surgical procedure to instrument the fetus with an arterial catheter and place a catheter in utero for collection of amniotic fluid samples. Physiologic variables and behavioral changes indicative of pain were assessed, and amniotic fluid and blood samples from ewes and fetuses were collected for determination of drug concentrations at predetermined times., Results: Both protocols provided acceptable postoperative analgesia with no adverse effects observed in the ewes or fetuses. Compared with the buprenorphine protocol, the fentanyl protocol induced more profound analgesia, decreased the requirement for isoflurane during surgery, and was associated with a shorter anesthesia recovery time. Fetal indices did not differ significantly between the 2 analgesic protocols., Conclusions and Clinical Relevance: Results indicated that both protocols provided acceptable analgesia. However, the fentanyl protocol was superior in regard to the extent of analgesia induced, inhalant-sparing effects, and anesthesia recovery time.

Critically appraised topics (CATs) are evidence syntheses that provide veterinary professionals with information to rapidly address clinical questions and support the practice of evidence-based veterinary medicine (EBVM). They also have an important role to play in both undergraduate and post-registration education of veterinary professionals, in research and knowledge gap identification, literature scoping, preparing research grants and informing policy. CATs are not without limitations, the primary one relating to the rapid approach used which may lead to selection bias or restrict information identified or retrieved. Furthermore, the narrow focus of CATs may limit applicability of the evidence findings beyond a specific clinical scenario, and infrequently updated CATs may become redundant. Despite these limitations, CATs are fundamental to EBVM in the veterinary profession. Using the example of a dog with osteoarthritis, the five steps involved in creating and applying a CAT to clinical practice are outlined, with an emphasis on clinical relevance and practicalities. Finally, potential future developments for CATs and their role in EBVM, and the education of veterinary professionals are discussed. This review is focused on critically appraised topics (CATs) as a form of evidence synthesis in veterinary medicine. It aims to be a primary guide for veterinarians, from students to clinicians, and for veterinary nurses and technicians (hereafter collectively called veterinary professionals). Additionally, this review provides further information for those with some experience of CATs who would like to better understand the historic context and process, including further detail on more advanced concepts. This more detailed information will appear in pop-out boxes with a double-lined surround to distinguish it from the information core to producing and interpreting CATs, and from the boxes with a single line surround which contain additional resources relevant to the different parts of the review., (Copyright © 2020 Brennan, Arlt, Belshaw, Buckley, Corah, Doit, Fajt, Grindlay, Moberly, Morrow, Stavisky and White.)

Macrolides are important antimicrobials frequently used in human and veterinary medicine in the treatment of pregnant women and pregnant livestock. They may be useful for the control of infectious ovine abortion, which has economic, animal health, and human health impacts. In this study, catheters were surgically placed in the fetal vasculature and amnion of pregnant ewes at 115 (±2) days of gestation. Ewes were given a single dose of 2.5 mg/kg tulathromycin subcutaneously, and drug concentrations were determined in fetal plasma, maternal plasma, and amniotic fluid at 4, 8, 12, 24, 36, 48, 72, 144, and 288 hr after drug administration. Pharmacokinetic parameters in maternal plasma were estimated using noncompartmental analysis and were similar to those previously reported in nonpregnant ewes. Tulathromycin was present in fetal plasma and amniotic fluid, indicating therapeutic potential for use against organisms in these compartments, though concentrations were lower than those in maternal plasma. Time-course of drug concentrations in the fetus was quite different than that in the ewe, with plasma concentrations reaching a plateau at 4 hr and remaining at this concentration for the remainder of the sampling period (288 hr), raising questions about how tulathromycin may be transported into or metabolized and eliminated by the fetus., (© 2019 John Wiley & Sons Ltd.)

The objective of this study was to determine the likelihood that swine treated with flunixin meglumine could contaminate their environment, which could cause untreated swine housed in the same pen to ingest or absorb enough drug to be detected in their urine. Currently, any detectable level of flunixin found in the urine of pigs exhibited at livestock shows in Texas can disqualify the exhibitor. We conducted 2 trials in this study. The first, a pilot trial, placed pigs in 2 pens, with each pen housing a pig that did not receive a drug and a treated pig that received 2.2 mg/kg of flunixin intramuscularly. This trial demonstrated that transfer of the drug from treated to untreated pigs housed in close proximity was possible. The second trial was conducted using 10 pens, with a treated and untreated pig in each pen. Each pig receiving treatment was randomly selected and administered 2.2 mg/kg of flunixin intramuscularly; then, urine and plasma were collected from all swine for 10 d. Flunixin was detected at or above the limit of detection of 0.1 ng/mL in the urine of all treated and untreated pigs throughout the 10-d trial. Treated pigs had higher urine levels of flunixin than their untreated pen mates for 4 d post-treatment ( P < 0.0001), but there was no statistical difference between pen mates during the last 5 d of the trial, making it impossible to differentiate treated from untreated pigs., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Objective: To determine oxytetracycline concentrations in plasma and in fluid from Corynebacterium pseudotuberculosis (CPT)-inoculated tissue chambers (used as experimental abscess models) and uninoculated (control) tissue chambers in sheep after IM or local administration of the drug and to investigate whether CPT growth was reduced or eliminated by these treatments., Animals: 10 clinically normal female sheep., Procedures: Sterile tissue chambers were surgically implanted in both paralumbar fossae of each sheep; ≥ 2 weeks later (day -6), 1 randomly selected chamber was inoculated with CPT, and the opposite chamber was injected with sterile growth medium. Sheep received oxytetracycline IM (n = 5) or by percutaneous injection into CPT-inoculated (4) or uninoculated (1) chambers on day 0. Tissue fluid from each chamber and venous blood samples for plasma collection were obtained at predetermined times over 6 days for bacterial counts (tissue chambers) and analysis of oxytetracycline concentrations (tissue chambers and plasma). Sheep were euthanized on day 6. Regional lymph nodes were collected bilaterally from each sheep for culture., Results: Measurable concentrations of oxytetracycline were present in each chamber throughout the study, regardless of administration route or presence of CPT. No CPT growth was detected after the 48-hour time point in inoculated chambers injected with oxytetracycline; however, CPT was isolated from all inoculated chambers throughout the study after IM drug administration. One regional lymph node (ipsilateral to a CPT-inoculated, oxytetracycline-injected chamber with no CPT growth after 48 hours) was culture positive for CPT., Conclusions and Clinical Relevance: Intralesional administration of oxytetracycline may eliminate growth of CPT locally, but complete elimination of the organism remains difficult.

Recent state and federal legislative actions and current recommendations from the World Health Organization seem to suggest that, when it comes to antimicrobial stewardship, use of antimicrobials for prevention, control, or treatment of disease can be ranked in order of appropriateness, which in turn has led, in some instances, to attempts to limit or specifically oppose the routine use of medically important antimicrobials for prevention of disease. In contrast, the AVMA Committee on Antimicrobials believes that attempts to evaluate the degree of antimicrobial stewardship on the basis of therapeutic intent are misguided and that use of antimicrobials for prevention, control, or treatment of disease may comply with the principles of antimicrobial stewardship. It is important that veterinarians and animal caretakers are clear about the reason they may be administering antimicrobials to animals in their care. Concise definitions of prevention, control, and treatment of individuals and populations are necessary to avoid confusion and to help veterinarians clearly communicate their intentions when prescribing or recommending antimicrobial use.

The purpose of this study was to determine if concentrations of chlortetracycline could be detected in fetal plasma or tissues after administering an oral dose of chlortetracycline (CTC; 500 mg/head/day) reported to be effective in controlling Campylobacter spp. abortions. Five pregnant ewes were administered 250 mg/head twice a day (total dose 500 mg/hd/d) for 7 days. On the beginning of day 7, intravenous catheters were surgically implanted or inserted into the fetus and dam. Plasma samples were collected from the ewe and fetus at various time points before and up to 36 hr after the last dose of CTC. All ewes were then sacrificed, and tissues were harvested from the fetus for drug analysis. Concentrations of CTC in maternal plasma were consistent with our previous study and below the minimum inhibitory concentration of Campylobacter abortion isolates. Concentrations of CTC were below the limit of detection in three of five fetal plasma samples and all of the placenta, amniotic fluid, and fetal stomach contents. Low concentrations were detectable in fetal kidney and liver, suggesting that CTC reaches the fetus, although at a variable and low ratio when compared to maternal concentrations., (© 2017 John Wiley & Sons Ltd.)

Background: Tritrichomonas foetus is a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option. The objectives of this study were twofold. The first objective was to demonstrate effectiveness for metronidazole treatment of a bull under ideal conditions and with an optimized treatment regime. This type of study with a single subject is often referred to as an n-of-1 or single subject clinical trial. The second objective of the current study was to review the scientific basis for the banning of metronidazole for use in Food Animals by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA)., Results: Results from an antimicrobial assay indicated that metronidazole at a concentration of 0.5 μg/mL successfully eliminated in vitro protozoal growth of bovine Tritrichomonas foetus. The estimated effective intravenous dose was two treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested positive for Tritrichomonas foetus culture at weekly intervals for 5 weeks prior to treatment was negative for Tritrichomonas foetus culture at weekly intervals for five consecutive weeks following this treatment regimen. An objective evaluation of the published evidence on the potential public health significance of using metronidazole to treat Tritrichomonas foetus in bulls provides encouragement for veterinarians and regulators to consider approaches that might lead to permitting the legal use of metronidazole in bulls., Conclusion: The study demonstrated successful inhibition of Tritrichomonas foetus both in vitro and in vivo with metronidazole. The current status of metronidazole is that the Animal Medicinal Drug Use Clarification Act of 1994 prohibits its extra-label use in food-producing animals. Veterinarians and regulators should consider approaches that might lead to permitting the legal use of metronidazole in bulls.

Background: Previously we showed therapeutic efficacy of unprotected miR-124 in preclinical murine models of glioblastoma, including in heterogeneous genetically engineered murine models by exploiting the immune system and thereby negating the need for direct tumor delivery. Although these data were promising, to implement clinical trials, we required a scalable formulation that afforded protection against circulatory RNases., Methods: We devised lipid nanoparticles that encapsulate and protect the miRs from degradation and provide enhanced delivery into the immune cell compartment and tested in vivo antitumor effects., Results: Treatment with nanoparticle-encapsulated miR-124, LUNAR-301, demonstrated a median survival exceeding 70 days, with an associated reversal of tumor-mediated immunosuppression and induction of immune memory. In both canine and murine models, the safety profile of LUNAR-301 was favorable., Conclusions: For the first time, we show that nanoparticles can direct a therapeutic response by targeting intracellular immune pathways. Although shown in the context of gliomas, this therapeutic approach would be applicable to other malignancies., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

A scoping review was conducted to identify modifiable non-antimicrobial factors to reduce the occurrence of antimicrobial resistance in cattle populations. Searches were developed to retrieve peer-reviewed published studies in animal, human and in vitro microbial populations. Citations were retained when modifiable non-antimicrobial factors or interventions potentially associated with antimicrobial resistance were described. Studies described resistance in five bacterial genera, species or types, and 40 antimicrobials. Modifiable non-antimicrobial factors or interventions ranged widely in type, and the depth of evidence in animal populations was shallow. Specific associations between a factor or intervention with antimicrobial resistance in a population (e.g. associations between organic systems and tetracycline susceptibility in E. coli from cattle) were reported in a maximum of three studies. The identified non-antimicrobial factors or interventions were classified into 16 themes. Most reported associations between the non-antimicrobial modifiable factors or interventions and antimicrobial resistance were not statistically significant (P > 0·05 and a confidence interval including 1), but when significant, the results were not consistent in direction (increase or decrease in antimicrobial resistance) or magnitude. Research is needed to better understand the impacts of promising modifiable factors or interventions on the occurrence of antimicrobial resistance before any recommendations can be offered or adopted.

The AAVMC has prioritized diversity as one of its core values. Its DiVersity Matters initiative is helping veterinary medicine prepare for the changing demographics of the United States. One example of the changing demographics is the growing Hispanic population. In 2013, the Texas A&M University College of Veterinary Medicine & Biomedical Sciences responded to the needs of this growing sector by introducing medical Spanish into the core curriculum for Doctor of Veterinary Medicine (DVM) students. The medical Spanish course takes place over 5 weeks during the second year of the curriculum, and is composed of lectures and group learning. While this may seem like a very compressed time frame for language learning, our goal is to provide students with basic medical vocabulary and a limited number of useful phrases. In this paper, we outline the implementation of a medical Spanish course in our curriculum, including our pedagogical approaches to the curricular design of the course, and an explanation of how we executed these approaches. We also discuss the successes and challenges that we have encountered, as well as our future plans for the course. We hope that the successes and challenges that we have encountered can serve as a model for others who plan to introduce a foreign language into their curriculum as a component of cultural competency.

Background: Large animal veterinarians carry drugs in their practice vehicles in storage areas that are not typically refrigerated. The most common upper limits of manufacturers' storage temperatures for United States (U.S.)-approved non-refrigerated drugs are 25 or 30 °C. Because ambient temperatures in many locations in the U.S. exceed these temperatures during the summer, we measured storage area temperatures over 4 months in the summer of 2013 to evaluate the extent to which labeled storage temperatures are exceeded., Methods: A convenience sample of 12 vehicles from 5 central Texas practices and 12 vehicles from 4 south central Nebraska practices was used. Temperatures were recorded in one drug storage compartment in each vehicle from May 15 - September 16, 2013, at 15-minute intervals using a self-contained, battery operated temperature recording device., Results: The highest temperatures recorded in a storage unit were 54.4 and 47.7 °C in Texas and Nebraska, respectively. The mean temperature recorded across all 24 storage units was 29.1 °C, with a mean of 26.9 °C in Nebraska and 31.4 °C in Texas. In Nebraska, at least one temperature over 25 °C was recorded on a mean of 111/124 days and a mean of 63 % of total logger readings. In Texas, temperatures over 25 °C were recorded on a mean of 123/124 days and a mean of 95 % of total logger readings., Conclusions: Temperatures in storage units in participating veterinary practice vehicles exceeded labeled drug storage temperatures a significant portion of the summer of 2013. More research is needed to determine whether these excursions above the manufacturers' recommended storage temperatures alter efficacy of stored drugs.

The objectives of this study were to determine plasma concentrations and pharmacokinetic parameters of tulathromycin after a single subcutaneous administration in the cervical region in sheep using the cattle labeled dose of 2.5 mg/kg. Six adult healthy ewes were administered tulathromycin on day 0. Blood samples were collected just prior to dosing and at selected time points for 360 h. Plasma samples were analyzed to determine tulathromycin concentrations, and noncompartmental analysis was performed for pharmacokinetic parameters. The mean maximum plasma concentration was 3598 ng/mL, the mean time to maximum concentration was 1.6 h, and the apparent elimination half-life ranged from 68.1 to 233.1 h (mean 118 h). When comparing our results to goats and cattle, it appears sheep are more similar to cattle in regard to the concentrations observed and pharmacokinetic parameters. In summary, the pharmacokinetics of tulathromycin in sheep appear to be similar enough to those in goats and cattle to recommend similar dosing (2.5 mg/kg SC), assuming that the target pathogens have similar inhibitory concentrations., (© 2014 John Wiley & Sons Ltd.)

Background: Deep digital septic conditions represent some of the most refractory causes of severe lameness in cattle. The objective of this study was to determine the distribution of tulathromycin, gamithromycin and florfenicol into the synovial fluid of the metatarsophalangeal (MTP) joint of cattle after single subcutaneous administration of drug to evaluate the potential usefulness of these single-dose, long-acting antimicrobials for treating bacterial infections of the joints in cattle., Results: Twelve cross-bred beef cows were randomly assigned to one of the drugs. Following subcutaneous administration, arthrocentesis of the left metatarsophalangeal joint was performed at various time points up to 240 hours post-injection, and samples were analyzed for drug concentration. In synovial fluid, florfenicol pharmacokinetic parameters estimates were: mean Tmax 7 +/- 2 hours, mean t½ 64.9 +/- 20.1 hours and mean AUC0-inf 154.0 +/- 26.2 ug*h/mL. Gamithromycin synovial fluid pharmacokinetic parameters estimates were: mean Tmax 8 hours, mean t½ 77.9 +/- 30.0 hours, and AUC0-inf 6.5 +/- 2.9 ug*h/mL. Tulathromycin pharmacokinetic parameters estimates in synovial fluid were: Tmax 19 +/- 10 hours, t½ 109 +/- 53.9 hours, and AUC0-inf 57.6 +/- 28.2 ug h/mL., Conclusions: In conclusion, synovial fluid concentrations of all three antimicrobials were higher for a longer duration than that of previously reported plasma values. Although clinical data are needed to confirm microbiological efficacy, florfenicol achieved a synovial fluid concentration greater than the MIC90 for F. necrophorum for at least 6 days.

The objectives of this study were to determine plasma concentrations and pharmacokinetic parameters of feed-grade chlortetracycline (CTC) in sheep after oral administration of 80 or 500 mg/head daily, divided into two equal doses given at 12-h intervals for 8 days. These are the approved, and commonly used but unapproved, feed additive doses, respectively, in the United States for the prevention of ovine infectious abortion. Blood samples were collected just prior to dosing at 0, 12, 24, 72, 96, and 192 h, as well as 4, 8, 12, 24, and 36 h after the last dose, and noncompartmental pharmacokinetic analysis was performed to estimate elimination half-life and area under the plasma concentration-time curve (AUC). Mean observed maximum CTC concentrations (Cmax ) were 20.0 ng/mL (80 mg dose) and 101 ng/mL (500 mg dose). Mean apparent elimination half-life was 18 h (80 mg dose) and 20 h (500 mg dose). Although published data do not exist to estimate plasma CTC concentrations necessary for the prevention of ovine infectious abortion, concentrations reached in our study suggest that either the FDA-approved and FDA-unapproved dosages are not high enough or that the pharmacodynamic parameter relating preventive dose to pathogen minimum inhibitory concentrations is yet to be determined., (© 2014 John Wiley & Sons Ltd.)

Matrix metalloproteinase-9 is elevated within the acutely injured murine spinal cord and blockade of this early proteolytic activity with GM6001, a broad-spectrum matrix metalloproteinase inhibitor, results in improved recovery after spinal cord injury. As matrix metalloproteinase-9 is likewise acutely elevated in dogs with naturally occurring spinal cord injuries, we evaluated efficacy of GM6001 solubilized in dimethyl sulfoxide in this second species. Safety and pharmacokinetic studies were conducted in naïve dogs. After confirming safety, subsequent pharmacokinetic analyses demonstrated that a 100 mg/kg subcutaneous dose of GM6001 resulted in plasma concentrations that peaked shortly after administration and were sustained for at least 4 days at levels that produced robust in vitro inhibition of matrix metalloproteinase-9. A randomized, blinded, placebo-controlled study was then conducted to assess efficacy of GM6001 given within 48 hours of spinal cord injury. Dogs were enrolled in 3 groups: GM6001 dissolved in dimethyl sulfoxide (n = 35), dimethyl sulfoxide (n = 37), or saline (n = 41). Matrix metalloproteinase activity was increased in the serum of injured dogs and GM6001 reduced this serum protease activity compared to the other two groups. To assess recovery, dogs were a priori stratified into a severely injured group and a mild-to-moderate injured group, using a Modified Frankel Scale. The Texas Spinal Cord Injury Score was then used to assess long-term motor/sensory function. In dogs with severe spinal cord injuries, those treated with saline had a mean motor score of 2 (95% CI 0-4.0) that was significantly (P<0.05; generalized linear model) less than the estimated mean motor score for dogs receiving dimethyl sulfoxide (mean, 5; 95% CI 2.0-8.0) or GM6001 (mean, 5; 95% CI 2.0-8.0). As there was no independent effect of GM6001, we attribute improved neurological outcomes to dimethyl sulfoxide, a pleotropic agent that may target diverse secondary pathogenic events that emerge in the acutely injured cord.

Clinical specimens from dogs, cats, and horses were examined for the presence of obligate anaerobic bacteria. Of 4,018 specimens cultured, 368 yielded 606 isolates of obligate anaerobic bacteria (248 from dogs, 50 from cats, and 308 from horses). There were 100 specimens from 94 animals from which only anaerobes were isolated (25 dogs, 8 cats, and 61 horses). The most common sites tested were abdominal fluid (dogs and cats) and intestinal contents (horses). The most common microorganism isolated from dogs, cats, and horses was Clostridium perfringens (75, 13, and101 isolates, respectively). The MICs of amoxicillin with clavulanate, ampicillin, chloramphenicol, metronidazole, and penicillin were determined using a gradient endpoint method for anaerobes. Isolates collected at necropsy were not tested for antimicrobial susceptibility unless so requested by the clinician. There were 1/145 isolates tested that were resistant to amoxicillin-clavulanate (resistance breakpoint ≥ 16/8 μg/ml), 7/77 isolates tested were resistant to ampicillin (resistance breakpoint ≥ 2 μg/ml), 4/242 isolates tested were resistant to chloramphenicol (resistance breakpoint ≥ 32 μg/ml), 12/158 isolates tested were resistant to clindamycin (resistance breakpoint ≥ 8 μg/ml), 10/247 isolates tested were resistant to metronidazole (resistance breakpoint ≥ 32 μg/ml), and 54/243 isolates tested were resistant to penicillin (resistance breakpoint ≥ 2 μg/ml). These data suggest that anaerobes are generally susceptible to antimicrobial drugs in vitro.

Background: Administration of a phosphodiesterase three enzyme inhibitor (PDE3-I) in rodents and primates results in ovulation of immature oocytes. Concerns regarding inhibition of PDE3 enzymes that are expressed in heart and blood vessels discouraged further development of PDE3-Is as nonsteroidal contraceptives. Cilostazol (CLZ) is a PDE3A-I that is approved for medical indications in humans and has an additional effect of adenosine uptake inhibition that is believed to counterbalance the undesirable outcomes resulting from PDE inhibition., Study Design: Cycling mature female mice were treated with 7.5 or 15 mg CLZ, dimethyl sulfoxide or water beginning on the day of proestrus. Animals were placed with fertility-proven males after 3 days of treatment. Treatments were continued until 1 day after detection of a vaginal plug, and then females were monitored up to 30 days postbreeding to assess the effects of the compounds on pregnancy. Each of the treated female with CLZ was then remated with the same male and again monitored up to 30 days., Results: None of the CLZ-treated mice produced offspring, whereas all of the control animals maintained pregnancy and delivered normal pups (p<.0001). Remating of the previously CLZ-treated females exhibited normal pregnancies and gave birth to live offspring that were not different from the controls., Conclusion: CLZ is a potential nonsteroidal contraceptive agent that merits further evaluation in other mammals., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To determine the serologic and bacteriologic culture prevalence of Corynebacterium pseudotuberculosis infection in sheep and goats and the value of such assays for prediction of future development of caseous lymphadenitis (CL)., Design: Observational study., Animals: 919 goats and sheep in 3 herds in southwest Texas., Procedures: During an initial evaluation, serologic and bacteriologic culture status for CL was determined for all animals. Subsequently, animals were evaluated every 6 months for a 13-month period to detect external CL lesions. Affected animals in 2 herds were treated with tulathromycin or a control treatment; affected animals in 1 herd were culled. The value of assays for prediction of future development of CL lesions was determined., Results: The serologic prevalence of CL in herds at the start of the study ranged from 7.52% to 69.54%. The bacteriologic culture prevalence of CL ranged from 0% to 6.12% at the start of the study and 0% to 9.56% at the end of the study. Synergistic hemolysin inhibition results were poor predictors of future development of CL lesions in animals during the study period; however, animals with positive bacteriologic culture results for CL were more likely to develop lesions in the future than were animals with negative bacteriologic culture results., Conclusions and Clinical Relevance: Caseous lymphadenitis was detected in animals in this study despite prior management of affected animals in herds via culling. Use of a synergistic hemolysin inhibition test for management of CL may cause unnecessary culling of animals; treatment might allow retention of genetically valuable CL-affected animals in a herd without substantially increasing the prevalence of CL.

The objective of this study was to ascertain current teaching methods for antimicrobial resistance (AMR) in veterinary professional curricula and to find out what veterinary instructors consider to be prioritized subtopics related to AMR. The sampling frame was instructors in veterinary professional programs at US colleges of veterinary medicine who provide instruction about antibiotics or AMR in the disciplines of microbiology, pharmacology, public health, epidemiology, internal medicine, surgery, or related subjects. Identified instructors were invited to participate in an online survey of current teaching methods related to subtopics of AMR. From 1,207 invitations, 306 completed surveys were available for analysis (25% response rate) with the largest number of respondents stating their contact hours about antibiotics occur in the discipline of "medicine-food animal." The median contact time suggested for AMR in the core veterinary curriculum was 3-5 hours, and for antibiotics in general, 16-20 hours. Subtopics of AMR were prioritized based on respondents' indication that they use or would use various teaching tools. The most common teaching tool for all topics was projected text (i.e., slides or PowerPoint slides) and the least common were video clips, non-course Web sites, online modules, and laboratory experiments. Recommendations for identifying the priorities of AMR content coverage and learning outcomes are made.

Intramuscular injections of drugs and vaccines cause tissue damage and subsequent effects on tenderness and consumer acceptability of beef. In the 2007 National Market Cow and Bull Beef Quality Audit, 100% of plants reported fabricating subprimal cuts such as rib eyes and tenderloins from cow and bull carcasses. Dairy beef quality should therefore be a consideration when injections are given to dairy animals. The discussion about injection site reactions and tenderness has focused on vaccines and antimicrobial drugs with little concern for the effects of reproductive hormones. The objective of this study was to quantify antemortem the effects of semimembranosis/semitendinosis muscle injection of dinoprost and GnRH in lactating dairy cows by estimating the weight of tissue damaged and comparing that with a drug known to cause extensive tissue damage, flunixin meglumine. Tissue damage was estimated from previously reported equations for grams of muscle tissue damage based on area under the curve of serum concentrations of the muscle enzyme creatine kinase over time. Dinoprost and flunixin injection both caused a significantly increased estimate of muscle tissue damaged compared with needle only (P = 0.0351 and 0.0355, respectively). Dinoprost and flunixin caused a marginally significant increased muscle tissue damage compared with GnRH (P = 0.1394 and 0.1475, respectively). No statistically significant difference was found between the estimated weight of muscle tissue damaged by flunixin compared with dinoprost (P = 1.0000), or by saline compared with GnRH (P = 0.7736) or needle only (P = 0.4902). The assumption that reproductive hormones are less damaging than vaccines and antimicrobial drugs should be examined more closely, including postmortem evaluation of injection site lesions and effects on tenderness.

Objective: To determine current attitudes and practices related to pain and analgesia in cattle among US veterinarians in bovine practice and to identify factors associated with these attitudes and practices., Design: Web-based survey. Sample-3,019 US members of the American Association of Bovine Practitioners (AABP) with e-mail addresses., Procedures: Veterinarians were invited via e-mail to participate in a Web-based survey. Respondents replied to questions related to pain and analgesia and supplied personal, professional, and demographic information. Descriptive statistical analysis was performed, and associations among various factors were examined., Results: 666 surveys (25.5% response rate) were analyzed. Among common procedures and medical conditions of cattle listed on the survey, castration of dairy calves < 6 months old was subjectively estimated as causing the least pain; abdominal surgery, toxic mastitis, and dehorning of calves > 6 months old were assessed as causing the greatest pain. Respondents reported not providing analgesic drugs to approximately 70% of calves castrated at < 6 months of age. The most commonly administered analgesics were NSAIDs, local anesthetics, and α(2)-adrenergic receptor agonists. Significant associations were detected among respondent characteristics and pain ratings, percentages of cattle treated, and opinions regarding analgesia., Conclusions and Clinical Relevance: Results provide information on current attitudes and practices related to pain and analgesia in cattle among US veterinarians in bovine practice and can be considered in the development of policies and protocols for pain management in cattle. These data can be compared with those of future studies to examine changes over time.

This article reviews laws and regulations related to drug use in sheep and goats, with special reference to the United States. The discussion includes drug licensing procedures, legalities of extralabel drug use, withdrawal time estimation, and residues in sheep and goat tissues; it refers also to regulations related to organic production, dairy production, and compounding. Canadian and European regulations are mentioned. Veterinarians working with sheep and goats must be familiar with regulations governing use of drugs, to prevent legal action, fulfill their fiduciary responsibility to producers, and help protect and provide for a wholesome and safe food supply., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To determine the pharmacokinetics of gallium maltolate (GaM) after intragastric administration in adult horses., Animals: 6 adult horses., Procedures: Feed was withheld for 12 hours prior to intragastric administration of GaM (20 mg/kg). A single dose of GaM was administered to each horse via a nasogastric tube (time 0). Blood samples were collected at various time points from 0 to 120 hours. Serum was used to determine gallium concentrations by use of inductively coupled plasma-mass spectroscopy. Noncompartmental and compartmental analyses of serum gallium concentrations were performed. Pharmacokinetic models were selected on the basis of the Akaike information criterion and visual analysis of plots of residuals., Results: Serum concentration data for 1 horse were such that this horse was considered an outlier and excluded from noncompartmental and compartmental analyses. Noncompartmental analysis was used to determine individual pharmacokinetic parameters. A 1-compartment model with first-order input and output and lag time was selected as the best-fit model for the data and used to determine mean ± SD values for maximum observed serum concentration (0.28 ± 0.09 μg/mL), time of maximum concentration (3.09 ± 0.43 hours), time to the first measurable concentration (0.26 ± 0.11 hours), apparent elimination half-life (48.82 ± 5.63 hours), area under the time-concentration curve (20.68 ± 757 h•μg/mL), and apparent volume of distribution (73,493 ± 18,899 mL/kg)., Conclusion and Clinical Relevance: Further studies are necessary to determine the bioavailability of GaM after intragastric administration in adult horses.

Objective: To compare apparent prevalence and patterns of antimicrobial resistance in Campylobacter spp in feces collected from pigs reared with antimicrobial-free versus conventional production methods in 8 states in the Midwestern United States., Design: Cross-sectional study., Sample Population: 95 swine farms that used antimicrobial-free (n = 35) or conventional (60) production methods., Procedures: Fecal samples from 15 pigs/farm were collected. Biochemical and multiplex-PCR analyses were used to identify Campylobacter spp. The minimal inhibitory concentrations of erythromycin, azithromycin, ciprofloxacin, nalidixic acid, gentamicin, and tetracycline for these organisms were determined by use of a commercially available antimicrobial gradient strip. The data were analyzed by use of population-averaged statistical models., Results: Campylobacter spp were isolated from 512 of 1,422 pigs. A subset (n = 464) of the 512 isolates was available for antimicrobial susceptibility testing. The apparent prevalence of Campylobacter spp isolates from pigs on conventional farms (35.8%) and antimicrobial-free farms (36.4%) did not differ significantly. Resistances to azithromycin, erythromycin, and tetracycline were significantly higher on conventional farms (70.0%, 68.3%, and 74.5%, respectively) than antimicrobial-free farms (20.1%, 21.3%, and 48.8%, respectively). Resistances to azithromycin, erythromycin, and tetracycline declined as the number of years that a farm was antimicrobial-free increased., Conclusions and Clinical Relevance: Production method did not affect the apparent prevalence of Campylobacter spp on swine farms. However, antimicrobial-free farms had a significantly lower prevalence of antimicrobial resistance. Although cessation of antimicrobial drug use will lower resistance over time, investigation of other interventions designed to reduce resistance levels is warranted.

The objective of this longitudinal ecological study was to examine the relationship between the prevalence of antibiotic-resistant (AR) commensal Escherichia coli isolates from both monthly human wastewater and composite swine fecal samples and the concurrent aggregated monthly antibiotic use recorded within each host species in multi-site vertically integrated swine and human populations. In addition, human vocation (swine worker versus non-swine worker), swine production group, and season were examined as potential confounding variables. Human and swine E. coli isolates (n=2469 human and 2310 swine, respectively) were tested for antimicrobial susceptibility using a commercial broth microdilution system. In the human population, among swine workers the relative odds of tetracycline resistance were increased significantly for tetracycline (class) drug use at the third quartile and above of mean monthly dosage (MMD) (OR=1.8) as compared to the referent category (non-use). The relative odds of ciprofloxacin resistance were significantly increased for ciprofloxacin use in non-swine workers (OR=5.5) as compared to the referent (non-use). The relative odds of tetracycline resistance were increased significantly for chlortetracycline use in medicated feed for the upper tertile of MMD category (OR=2.9) as compared to the referent category (no use) across all swine production groups. While high variability among seasonal samples over the 3-year period was observed, no common seasonal trends relating to antibiotic use and prevalence of resistance over the 3-year period were apparent. The overall effects of concurrent human and swine antibiotic use on AR E. coli levels were inconsistent and modest in this study.

Accessing new knowledge and using it to make decisions is the foundation of evidence-based veterinary medicine (EBVM), the integration of best research evidence with clinical expertise and owner/manager values. Reflecting on our experience with an EBVM-based clinical pharmacology assignment during a clinical rotation, we present the justification for the addition of an EBVM assignment to the clinical (fourth) year at the College of Veterinary Medicine and Biomedical Sciences at Texas A&M University. We also present an in-depth analysis of the addition, recommendations for the assessment of this exercise as a method of improving evidence-based veterinary practice, and recommendations and implications for other instructors interested in adding EBVM-related learning to their professional curricula. We recommend adding EBVM skill practice in pre-clinical training, abbreviated exercises in EBVM skills on clinical rotations, and increased attention to critical-thinking skills in veterinary education.

Objective: To compare the effectiveness of 3 treatment regimens for small ruminants with caseous lymphadenitis., Design: Randomized clinical trial., Animals: 44 client-owned sheep and goats., Procedures: Aspirates were obtained from 48 lesions of 44 enrolled animals and submitted for bacterial culture. Animals were randomly assigned to 1 of 3 treatment groups. Treatment for group A (n = 15 lesions) consisted of opening, draining, and flushing the lesions and SC administration of procaine penicillin G. Treatment for group B (n = 15 lesions) consisted of closed-system lavage and intralesional administration of tulathromycin. Treatment for group C (n = 18 lesions) consisted of closed-system lavage and SC administration of tulathromycin. All animals were reexamined approximately 1 month after treatment, unless treatment failure was detected prior to that time., Results: 43 animals with lesions had positive results (Corynebacterium pseudotuberculosis) for bacterial culture. Proportions of lesions that had resolution of infection by 1 month after treatment did not differ significantly among the treatment groups (group A, 13/14 [92.9%]; 95% confidence interval [CI], 69.5% to 99.6%; group B, 10/12 [83.3%]; 95% CI, 54.9% to 97.1%; and group C, 14/17 [82.4%]; 95% CI, 59.1% to 95.3%)., Conclusions and Clinical Relevance: Acceptable alternatives to opening, draining, and flushing of lesions may exist for treatment of sheep and goats with caseous lymphadenitis. Use of tulathromycin and penicillin in this study constituted extralabel drug use, which would require extended withholding times before milk or meat of treated sheep and goats can be sold for human consumption.

This report describes the results of two efforts to gather data on the needs of veterinary pharmacology, whether academic or industrial, to better define the skills and competencies that graduate programs in veterinary pharmacology should endeavor to provide. Data collected from an on-line survey of the animal health industry were used to develop a workshop at the biennial meeting of the American Academy of Veterinary Pharmacology and Therapeutics. Lists of skills were developed and categorized, and differences among the skills identified by industry vs. academy were outlined. This report offers a blueprint for graduate education in veterinary pharmacology in terms of the types and details of skills and competencies to better prepare future veterinary pharmacologists.

Diets fed to feedlot cattle typically contain nutritional ingredients along with other substances intended for various purposes, including growth promotion and disease prevention and control. Questions often arise as to the nature of those feed additives, whether and how they are regulated, and what is legal or illegal. In this article, the author discusses regulations pertinent to the use of drugs in feedlot diets. The article includes a discussion of what a drug is, how drugs are approved in the United States, what uses of drugs in feedlot diets are legal or illegal, and what is on the horizon for future drug regulations.

Objective: To examine effects of danofloxacin and tilmicosin on continuously recorded body temperature in beef calves with pneumonia experimentally induced by inoculation of Mannheimia haemolytica., Animals: 41 Angus-cross heifers (body weight, 160 to 220 kg) without a recent history of respiratory tract disease or antimicrobial treatment, all from a single ranch., Procedure: Radiotransmitters were implanted intravaginally in each calf. Pneumonia was induced intrabronchially by use of logarithmic-phase cultures of M. haemolytica. At 21 hours after inoculation, calves were treated with saline (0.9% NaCl) solution, danofloxacin, or tilmicosin. Body temperature was monitored from 66 hours before inoculation until 72 hours after treatment. Area under the curve (AUC) of the temperature-time plot and mean temperature were calculated for 3-hour intervals and compared among treatment groups., Results: The AUCs for 3-hour intervals did not differ significantly among treatment groups for any of the time periods. Analysis of the mean temperature for 3-hour intervals revealed significantly higher temperatures at most time periods for saline-treated calves, compared with temperatures for antimicrobial-treated calves; however, we did not detect significant differences between the danofloxacin- and tilmicosin-treated calves. The circadian rhythm of temperatures before exposure was detected again approximately 48 hours after bacterial inoculation., Conclusions and Clinical Relevance: Danofloxacin and tilmicosin did not differ in their effect on mean body temperature for 3-hour intervals but significantly decreased body temperature, compared with body temperature in saline-treated calves. Normal daily variation in body temperature must be considered in the face of respiratory tract disease during clinical evaluation of feedlot cattle.

The author's interpretation of some of the regulations involved in drug selection and usage by bovine veterinarians has been presented here. If necessary, the practitioner should address further questions to the appropriate regulatory agencies. The role of the veterinarian in protecting the US food supply has never been more critical, and familiarity with the applicable regulations regarding drugs used in food animals is an important component of the food animal veterinarian's knowledge base.

Pneumonia caused by Pasteurella (Mannheimia) haemolytica was induced in weaned beef heifer calves, approximately 6 months of age. Calves were treated at 20 h after challenge with therapeutic doses of danofloxacin or tilmicosin. Peripheral blood neutrophils were collected at 3, 24 and 48 h after treatment. The ex vivo effects on neutrophil function, neutrophil apoptosis, and hematological parameters were examined, as was the effect on percentage lung consolidation. Neutrophil function assays included random migration under agarose, cytochrome C reduction, iodination, Staphylococcus aureus ingestion, chemotaxis, and antibody-dependent and antibody-independent cell-mediated cytotoxicity. Apoptosis was determined using a cell death detection kit. Killing was performed at 72 h after treatment. Statistical comparisons were made among the three groups of challenged-treated animals: saline, danofloxacin, and tilmicosin. Comparisons were also made between nonchallenged nontreated animals (NCH) and challenged saline-treated animals. There were no significant differences for any of the neutrophil function assays or neutrophil apoptosis among the challenged-treated groups. This suggests that danofloxacin and tilmicosin have no clinically significant effects on neutrophil function or apoptosis. There were also no significant differences in percentage lung consolidation among the challenged-treated groups. Significant differences were found between the NCH calves and the challenged saline-treated calves in several neutrophil assays, which were attributed to effects of P. haemolytica infection.

The small ruminant practitioner has a small arsenal of approved drugs in the United States, so the practitioner must be familiar with the laws and regulations related to extra label use. Drugs can be used extra label in food animals only under specific circumstances and can be used only for therapeutic purposes. Drugs that are illegal in small ruminants include chloramphenicol; clenbuterol; diethylstilbestrol; dimetridazole, ipranidazole, and other nitroimidazoles such as metronidazole; dipyrone; fluoroquinolones; glycopeptides; nitrofurans; furazolidone; and extra label use of medication in feed. It is also illegal to use any drug that results in residues above established tolerances or safe levels.

This article reviews some of the issues surrounding antimicrobial use in treating diseases that cause lameness in cattle. The discussion includes sections on selection of an antimicrobial, regimen design, and medication of multiple animals. Pathogen susceptibility testing is covered, along with empiric selection of antimicrobials. Other issues covered include regional perfusion and topical application of antimicrobials, antimicrobials in footbaths and in feed, and withdrawal time estimates.