Pharmacokinetics of oral firocoxib in un-weaned calves.

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 Cmax was 0.9 µg/ml (range 0.570-1.254), and Tmax was estimated to be 7 h (range 4-8 h). The estimated T1/2 was 15.3 h. The pharmacokinetics of firocoxib after oral dosing are similar to those in dogs, with the exception of a T1/2 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.

Plasma disposition of ceftazidime in healthy neonatal foals following intravenous and intramuscular administration.

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 t1/2 was 2 h and median AUC0-last was 364 µg h/ml for both IV and IM administration. Median Cmax after IM administration was 101 µg/ml, with a median Tmax 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.

Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs.

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.

Pharmacokinetics of tulathromycin in fetal sheep and pregnant ewes.

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.

Metronidazole for the treatment of Tritrichomonas foetus in bulls.

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.

Developing Cultural Competence through the Introduction of Medical Spanish into the Veterinary Curriculum.

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.

Temperatures of storage areas in large animal veterinary practice vehicles in the summer and comparison with drug manufacturers' storage recommendations.

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.

Synovial fluid pharmacokinetics of tulathromycin, gamithromycin and florfenicol after a single subcutaneous dose in cattle.

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.

Survey of instructors teaching about antimicrobial resistance in the veterinary professional curriculum in the United States.

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.

Application and Interpretation of Antimicrobial Susceptibility Testing.

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.

Benefits and challenges of creating veterinary antibiograms for empiric antimicrobial selection in support of antimicrobial stewardship and advancement of one-health goals.

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).

Using telehealth clinical case vignettes to enhance clinical confidence and competence in veterinary students.

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.

Analgesic drug administration and attitudes about analgesia in cattle among bovine practitioners in the United States.

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.

Patterns of antimicrobial drug use in veterinary primary care and specialty practice: A 6-year multi-institution study.

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/ß-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.

Pharmacokinetics of gallium maltolate after intragastric administration in adult horses.

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.

Prevalence and patterns of antimicrobial resistance in Campylobacter spp isolated from pigs reared under antimicrobial-free and conventional production methods in eight states in the Midwestern United States.

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.

A Comparison of Buprenorphine, Sustained release Buprenorphine, and High concentration Buprenorphine in Male New Zealand White Rabbits.

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-3ß-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.

Critically Appraised Topics (CATs) in Veterinary Medicine: Applying Evidence in Clinical Practice.

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.

Can the use of older-generation beta-lactam antibiotics in livestock production over-select for beta-lactamases of greatest consequence for human medicine? An in vitro experimental model.

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 ß-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 ß-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.

Comparison of analgesic efficacy and fetal effects between transdermal administration of fentanyl and intramuscular administration of buprenorphine in pregnant sheep.

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.