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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).

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.)

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.

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.)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.