Randomized placebo-controlled trial of feline-origin Enterococcus hirae probiotic effects on preventative health and fecal microbiota composition of fostered shelter kittens.

Introduction: Diarrhea is the second most common cause of mortality in shelter kittens. Studies examining prevention strategies in this population are lacking. Probiotics are of particular interest but studies in cats are largely limited to healthy adults or those with induced disease. Only one study in domestic cats describes the use of host-derived bacteria as a probiotic. We previously identified Enterococcus hirae as a dominant species colonizing the small intestinal mucosa in healthy shelter kittens. Oral administration of a probiotic formulation of kitten-origin E. hirae (strain 1002-2) mitigated the increase in intestinal permeability and fecal water loss resulting from experimental enteropathogenic E. coli infection in purpose-bred kittens. Based on these findings, we hypothesized that administration of kitten-origin E. hirae to weaned fostered shelter kittens could provide a measurable preventative health benefit. Methods: We conducted a randomized, placebo-controlled, blinded clinical trial to determine the impact of a freeze-dried E. hirae probiotic on body weight gain, incidence of diarrhea, carriage of potential diarrheal pathogens, and composition of the intestinal microbiota in weaned fostered shelter kittens. Results: One-hundred thirty kittens completed the study. Fifty-eight kittens received the probiotic and 72 received the placebo. There were no significant differences in age, weight upon initiation of the study, number of days in the study, average daily gain in body weight, or weight at completion of the study. Kittens treated with E. hirae were 3.4 times less likely to develop diarrhea compared to kittens treated with placebo (odds ratio = 0.294, 95% CI 0.109-0.792, p = 0.022). A significant impact of E. hirae was not observed on the presence or abundance of 30 different bacterial, viral, protozoal, fungal, algal, and parasitic agents in feces examined by qPCR. With exception to a decrease in Megamonas, administration of the E. hirae probiotic did not alter the predominant bacterial phyla present in feces based on 16S rRNA gene amplicon sequencing. Discussion: Decreased incidence of diarrhea associated with preventative administration of E. hirae to foster kittens supports a rationale for use of E. hirae for disease prevention in this young population at high risk for intestinal disease though additional studies are warranted.

Availability of Didactic and Experiential Learning Opportunities in Veterinary Practice at US Pharmacy Programs.

Objective. To explore the availability of veterinary pharmacy didactic and experiential learning opportunities in US pharmacy programs.Methods. A 23-item questionnaire was sent to subscribers of the American Association of Colleges of Pharmacy Curriculum and Pharmacy Practice listservs, which reach 2,098 participants and 141 pharmacy programs. The Fisher exact test was used to evaluate the association of offering a didactic course and accepting credit from an outside program for veterinary pharmacy course and between pharmacy programs offering a veterinary didactic course and being affiliated with a Doctor of Veterinary Medicine program. All analyses were conducted using SPSS, version 26.Results. Questionnaire response rate was 61% (86/141). Twenty seven percent (23/86) of pharmacy programs reported offering a didactic veterinary pharmacy course and 60% (52/86) reported having experiential rotation opportunities. Pharmacy programs that do not offer a veterinary pharmacy course, were not more or less likely to accept outside credit to gain didactic knowledge. Pharmacy programs geographically associated with a veterinary school were more likely to offer didactic as well as experiential opportunities.Conclusion. Pharmacy programs were twice as likely to have experiential opportunities in veterinary pharmacy compared to didactic opportunities, leaving room for curricular development. With most graduating pharmacists choosing to work in the community pharmacy setting and the growth of veterinary pharmacy at several national corporate pharmacy chains, it would be advisable for pharmacy programs to expose students to veterinary pharmacy whether as a didactic course and/or an experiential rotation.

Characterization of Veterinary Pharmacy and Pharmacology Literature and its Availability to Pharmacy Education.

Objective. To characterize the veterinary pharmacy and pharmacology literature cited by veterinary drug monographs and journal articles and describe the database indexing and availability of this literature in libraries serving pharmacy schools. Methods. Citations in American Academy of Veterinary Pharmacology and Therapeutics monographs, Journal of Veterinary Pharmacology and Therapeutics (JVPT) articles, and Plumb's Veterinary Drug Handbook, Eighth Edition (Plumb's) were analyzed for publication type and age. Three zones of cited journals were determined by Bradford's Law of Scattering based on citation counts. Results. Monographs most often cited journal articles (1886 [64.7%]), unpublished "grey" literature (632 [21.7%]), and books (379 [13.0%]), but only a few cited proceedings (16 [0.5%]). In JVPT, articles predominated (9625 [91.9%]). Articles comprised 54.8% (1,959) of Plumb's citations; proceedings, 27.0%; books, 15.7%; and grey literature, 2.5%. The age of cited items varied, with 17.1% of monograph citations less than five years old, compared to 26.3% of cited items in JVPT and 40.5% of cited items in Plumb's being less than five years old. Zone 1 consisted of three veterinary journals for monographs, four veterinary journals for Plumb's, and 16 veterinary and human journals for JVPT. Indexing coverage was above 92% in Web of Science, Scopus, and PubMed for zone 1 and 2 journals. Libraries serving both pharmacy and veterinary education programs subscribe to 95% of zone 1 journals, while libraries serving pharmacy education at institutions without a veterinary program subscribe to an average of 59% of zone 1 journals. Conclusion. Veterinary pharmacy and pharmacology literature relies on journals from human and veterinary practice, veterinary proceedings, and, less often, books and drug manufacturer information. Libraries supporting pharmacy programs could contribute to the education of future pharmacists who will be filling veterinary prescriptions by increasing access to this literature.

Baseline Knowledge of Potential Pet Toxins among the US General Public.

In 2014, the American Society for the Prevention of Cruelty toAnimals Animal Poison Control Center fielded more than 167,000cases of potential nonhuman animal toxicosis. Concomitantly, thereremain limited free and reputable veterinary toxicology resourcesavailable for companion-animal (pet) caregivers (owners) seekingassistance and advice about potentially harmful exposures inanimals. The objective of this study was to assess pet toxicantknowledge among a representative sample of Americans andgauge the need for additional toxicology resources. The studyinvolved a survey designed to capture participants' ability to identifypotential animal toxicants and what resource they would use ifan accidental toxic ingestion occurred. Participants were ableto correctly identify 52% of potential pet toxins. Women, olderparticipants and participants from the South expressed moreconcern about each potential pet poison. Approximately halfof participants indicated they would consult a veterinarian andwhereas most others indicated they would search the Internet formore information about pet toxicology. The findings suggest moreveterinary poisoning education is needed for pet owners to be ableto accurately distinguish potential pet toxicants from nontoxicants.

Compounding and Extralabel Use of Drugs in Exotic Animal Medicine.

Extralabel drug use is the use of a Food and Drug Administration (FDA)-approved drug in a manner different from what is stipulated on the approved label. Compounding is the process of preparing a medication in a manner not indicated on the label to create a formulation specifically tailored to the needs of an individual patient. Extralabel drug use and compounding are vital aspects of safe and effective drug delivery to patients in exotic animal practice. There are few FDA-approved drugs for exotic animal species, and many approved drugs for other species are not available in suitable formulations for use in exotic animals.

Pharmacists' Knowledge of Veterinary Pharmacotherapy and the Impact of an Educational Intervention.

Background: To date, there is very limited data regarding pharmacists' preparedness to handle animal prescriptions. No previous studies exist examining the impact of a veterinary-pharmacy-focused educational intervention. Objective: To assess pharmacists' baseline knowledge of veterinary pharmacotherapy, as relevant to their professional responsibilities, and assess the impact of a piloted educational program. Methods: Two studies were conducted. The first study involved a statewide assessment of pharmacists' knowledge of veterinary pharmacotherapy; the second study assessed the impact of an educational intervention to improve pharmacists' veterinary pharmacotherapy knowledge base. Participants in the pilot study were assessed via pretest and posttest. Results: The statewide sample of participants (n = 602) received a mean score of 5.9 (SD = 2.6) on a 17-item questionnaire. There were no discernible differences in participants' knowledge based on the subject matter of the question (pathophysiology, dosing, counseling, compounding, legality, and toxicology). Using the same 17-item questionnaire, pilot study participants (n = 60) received a mean score of 5.2 (SD = 2.4) on the pretest and 16.6 (SD = 0.7) on the posttest. Conclusion: The findings of this study suggest that a substantial portion of pharmacists lack the knowledge needed to process and dispense the veterinary prescriptions most commonly encountered in community pharmacies. Furthermore, this study shows that implementation of an educational intervention can increase pharmacists' knowledge of core concepts necessary to safely care for animal patients.

Baseline knowledge of potential pet toxins: a survey of pharmacists

Background: Consumer expenditures on their family pets are rapidly increasing, part of which can be attributed to prescription and OTC medications. In turn, community pharmacies are seeking and receiving an increased number of prescriptions for animals. Community pharmacists’ ability to safely care for animal patients is relatively unexplored. Human medications, their normal dosing and even medication excipients could be lethal in some animal patients. Objective: The overarching objective of this study was to assess pharmacists’ baseline knowledge of potential pet poisons. Methods: The sample consisted of licensed pharmacists registered with the North Carolina Board of Pharmacy. The Pet Toxins Survey (PTS), a survey consisting of 25 potential pet toxins, was administered during October and November 2015. Analyses consisted of calculating descriptive statics (including graphical summaries to test for normality), and inferential statistics (two-tailed t-tests and ANOVAs) to compare responses across demographic variables. Results: A 6.3% response rate was obtained. After selecting either a dog or a cat to establish a frame of reference, participants in this study were able to correctly identify 15 of the 25 listed items as toxic to a pet (60% accuracy). Participants did not express adequate concern for the ingestion of several potential toxins. This includes potential excipients found in medication formulations such as xylitol, tea tree oil and caffeine. Female participants and those age 50 years and older were more likely to indicate concern for each potential toxin. There was no significant difference observed in responses based on the pharmacists’ work setting. Conclusions: The findings of this investigation suggest that pharmacists are deficient in their understanding of veterinary toxicology. Given the rise of community pharmacists caring for animal patients, it’s paramount that pharmacists be able to confidently distinguish potential pet toxins from non-toxins. It is also important that pharmacists receive a better understanding of what exposures require immediate action and what action should be taken (AU)

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Pharmacokinetics and toxicity of subcutaneous administration of carboplatin in poloxamer 407 in a rodent model pilot study.

The objectives of this study were to assess the pharmacokinetics and safety of subcutaneously delivered carboplatin in poloxamer 407 in rats. Carboplatin (5mg/rat) in 0.5ml poloxamer 407 (1.0 ml total volume) was administered subcutaneously in a right subcutaneous perineal incision in all 12 treatment rats. Three control rats received 1.0 ml of poloxamer 407. Total platinum was measured in plasma q24hrs from 0 to 168hrs. Protein-unbound platinum was measured in plasma at 168hrs. After sacrifice on day 7, total platinum was determined in wound bed muscle. Platinum concentrations in all samples were measured by ICP-MS. Wounds were visually assessed daily for 7 days. Perineal tissues (full wound bed including muscle, subcutis, skin) were assessed histologically and scored. Total platinum was detectable in plasma from 24 to 168 hrs. Total plasma platinum AUC and Cmax were 9,165.3 ng/mL•h and 129.4 ng/mL. Day 7 total platinum concentration in muscle was approximately 10-fold higher than total plasma platinum concentration. No unbound platinum was detected in plasma samples at 168 hours. No wound healing complications were detected at any time point, nor was tissue necrosis observed histologically. The results of this study suggest that subcutaneous carboplatin in poloxamer 407 can be used in vivo providing direct tissue exposure to carboplatin without significant local effects or systemic absorption and without wound healing complications.

Veterinary Compounding: Regulation, Challenges, and Resources.

The spectrum of therapeutic need in veterinary medicine is large, and the availability of approved drug products for all veterinary species and indications is relatively small. For this reason, extemporaneous preparation, or compounding, of drugs is commonly employed to provide veterinary medical therapies. The scope of veterinary compounding is broad and focused primarily on meeting the therapeutic needs of companion animals and not food-producing animals in order to avoid human exposure to drug residues. As beneficial as compounded medical therapies may be to animal patients, these therapies are not without risks, and serious adverse events may occur from poor quality compounds or excipients that are uniquely toxic when administered to a given species. Other challenges in extemporaneous compounding for animals include significant regulatory variation across the global veterinary community, a relative lack of validated compounding formulas for use in animals, and poor adherence by compounders to established compounding standards. The information presented in this article is intended to provide an overview of the current landscape of compounding for animals; a discussion on associated benefits, risks, and challenges; and resources to aid compounders in preparing animal compounds of the highest possible quality.

Baseline knowledge of potential pet toxins: a survey of pharmacists.

BACKGROUND: Consumer expenditures on their family pets are rapidly increasing, part of which can be attributed to prescription and OTC medications. In turn, community pharmacies are seeking and receiving an increased number of prescriptions for animals. Community pharmacists' ability to safely care for animal patients is relatively unexplored. Human medications, their normal dosing and even medication excipients could be lethal in some animal patients. OBJECTIVE: The overarching objective of this study was to assess pharmacists' baseline knowledge of potential pet poisons. METHODS: The sample consisted of licensed pharmacists registered with the North Carolina Board of Pharmacy. The Pet Toxins Survey (PTS), a survey consisting of 25 potential pet toxins, was administered during October and November 2015. Analyses consisted of calculating descriptive statics (including graphical summaries to test for normality), and inferential statistics (two-tailed t-tests and ANOVAs) to compare responses across demographic variables. RESULTS: A 6.3% response rate was obtained. After selecting either a dog or a cat to establish a frame of reference, participants in this study were able to correctly identify 15 of the 25 listed items as toxic to a pet (60% accuracy). Participants did not express adequate concern for the ingestion of several potential toxins. This includes potential excipients found in medication formulations such as xylitol, tea tree oil and caffeine. Female participants and those age 50 years and older were more likely to indicate concern for each potential toxin. There was no significant difference observed in responses based on the pharmacists' work setting. CONCLUSIONS: The findings of this investigation suggest that pharmacists are deficient in their understanding of veterinary toxicology. Given the rise of community pharmacists caring for animal patients, it's paramount that pharmacists be able to confidently distinguish potential pet toxins from non-toxins. It is also important that pharmacists receive a better understanding of what exposures require immediate action and what action should be taken.

Assessment of in vitro release of carboplatin from six carrier media.

OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media. SAMPLE 6 carboplatin-containing carrier media. PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen. RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours. CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.

Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections.

OBJECTIVE: To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections. DESIGN: Cross-sectional survey. SAMPLE: 71 veterinarians. PROCEDURES: An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance. RESULTS: Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns. CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals.

To compound or not to compound: a veterinary transdermal discussion.

Administering chronic medications to feline patients without the daily battle of oral and injectable medications is the holy grail of veterinary pharmacotherapy. For some medications, the transdermal route may be the solution. However, there are many considerations for determining if a medication will be safe for the patient and caregiver as well as effective when administered transdermally. A comprehensive checklist to assess the appropriateness of transdermal therapy is provided.

Doxycycline concentration over time after storage in a compounded veterinary preparation.

OBJECTIVE: To determine the concentration of doxycycline compounded from doxycycline hyclate tablets into liquid formulations for oral administration in veterinary species and stored for 28 days. DESIGN: Evaluation study. SAMPLE: Doxycycline hyclate tablets (100 mg) crushed and mixed with a 50:50 mixture of syrup and suspension vehicles for oral administration to produce 3 batches each of 2 doxycycline formulations: 33.3 and 166.7 mg/mL. PROCEDURES: Formulations were stored, protected from light, at room temperature (22° to 26°C [71.6° to 78.8°F]) and at a controlled cold temperature (refrigerated 2° to 8°C [35.6° to 46.4°F]). Doxycycline was extracted from the formulations, and concentration was measured by high-pressure liquid chromatography on days 0 (date of preparation), 1, 4, 7, 14, 21, and 28. Concentrations were compared with those of a US Pharmacopeial Convention reference standard. Formulation quality at each point was also assessed through color change, formulation consistency, and suspension uniformity. RESULTS: On days 0, 1, 4, and 7, the concentration of each formulation was within 90% to 110% of the reference standard (range, 93% to 109%), which was deemed acceptable. However, doxycycline concentrations had decreased dramatically by day 14 and remained low for the duration of the study period. Doxycycline concentrations on days 14, 21, and 28 were all < 20% (range, 14% to 18%) of the reference standard, and the quality of the formulations decreased as well. No effect of storage temperatures on doxycycline concentration was identified. CONCLUSIONS AND CLINICAL RELEVANCE: The concentration of doxycycline, compounded from commercial tablets in the vehicles evaluated to yield doses of 33.3 and 166.7 mg/mL, cannot be assured beyond 7 days.

Aqueous humor and plasma concentrations of a compounded 0.2% solution of terbinafine following topical ocular administration to normal equine eyes.

OBJECTIVE: To determine the transcorneal penetration and systemic absorption of a compounded 0.2% terbinafine solution following repeated topical administration to normal equine eyes. Sample population Six healthy adult horses with normal ocular examinations. PROCEDURES: One eye of each horse received 0.2 mL of a compounded 0.2% terbinafine solution every 4 h for seven doses. During the 1 h following administration of the final dose, multiple peripheral blood samples were obtained, and a single aqueous humor (AH) sample was collected at the end of the hour. AH and plasma concentrations of terbinafine were determined using high pressure liquid chromatography (HPLC). Stability of the formulation was assessed with HPLC analysis over a 14-day time period. RESULTS: Terbinafine was not detected in the AH or plasma of any horse at any time point. No signs of ocular irritation or systemic toxicity were noted in any horse at any time point. The solution was stable over 14 days. CONCLUSION: Topical ocular administration of compounded 0.2% terbinafine solution does not result in detectable AH or plasma levels following administration to normal equine eyes, suggesting its use for deep corneal or intraocular fungal infections in equine ophthalmology may be limited.

Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats.

Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2mg/kg) and a 95mg immediate-release RDZ capsule (mean 28.2mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.

Successful management of gastrointestinal pythiosis in a dog using itraconazole, terbinafine, and mefenoxam.

Medical therapy for pythiosis is hampered by a lack of efficacious drugs. The present report describes a case of canine gastrointestinal pythiosis in which lesions were resolved through the administration of itraconazole, terbinafine, and the agricultural fungicide mefenoxam. No substantial adverse effects occurred in association with administration of the latter compound. Additional studies are needed to evaluate the pharmacokinetics of mefenoxam and to further assess its tolerability and potential efficacy for the treatment of pythiosis in dogs.

Evaluation of intermittent infusion of bupivacaine into surgical wounds of dogs postoperatively.

Thirty-one dogs were randomised to receive intermittent wound infusion of bupivacaine or saline after surgery. Wound pressure sensitivity, pain scores, body temperature, heart rate, respiratory rate, analgesic drugs administered, time to walking and time to eating after surgery were recorded. Plasma bupivacaine concentrations were measured. The relative frequency distributions of the non-interventional and interventional pain scores, but not the relative frequency distributions of palpation pain scores or wound pressure sensitivity, were significantly different between groups following surgery. There was a significant difference between groups in the time to eating and in the amount and timing of analgesic drugs administered. Measured plasma bupivacaine concentrations demonstrated systemic absorption of the drug. Bupivacaine infusion into surgical wounds after surgery may improve post-operative recovery, but no effect on wound tenderness was demonstrated in this study.