OBJECTIVE To characterize antimicrobial prescribing patterns of clinicians and clinical services at a large animal veterinary teaching hospital and identify factors associated with antimicrobial prescribing. ANIMALS All large animals (ie, equids, bovids, sheep, goats, camelids, swine, and cervids) evaluated at the New Bolton Center hospital at the University of Pennsylvania from 2013 through 2018. PROCEDURES In a cross-sectional study design, data on antimicrobial use by clinicians and clinical services were collected from administrative and billing records. Multivariable regression modeling was performed to identify factors associated with antimicrobial prescribing patterns. RESULTS Antimicrobials and critically important antimicrobials of the highest priority were dispensed in 42.1% (9,853/23,428) and 24.0% (2,360/9,853) of visits, respectively, and these proportions differed significantly among clinicians. Per visit, the median (interquartile [25th to 75th percentile] range) number of animal-defined daily doses dispensed was 3.6 (0.8 to 11.1) and the mean (SD) number of antimicrobial classes dispensed was 2.0 (1.3). Patient species, age, affected body system, and duration of hospitalization as well as submission of specimens for bacterial culture were significantly associated with prescribing patterns. CONCLUSIONS AND CLINICAL RELEVANCE The frequency and quantity of antimicrobials prescribed differed significantly among clinicians within and across services, even for animals with clinical signs affecting the same body system. Patient- and visit-level factors explained some but not all of the heterogeneity in prescribing patterns, suggesting that other clinician-specific factors drove such practices. More research is needed to better understand antimicrobial prescribing patterns of clinicians, particularly in situations for which no antimicrobial use guidelines have been established.

OBJECTIVE To use a biopolymer delivery system to investigate the ability of interleukin (IL)-4 to recruit neutrophils into subcutaneous tissues of equids. ANIMALS 16 horses and 2 ponies. PROCEDURES Animals were assigned to 3 experiments (6/experiment). Effects of recombinant equine (Req) IL-4 (100, 250, or 500 ng/site) versus a positive control (ReqIL-8; 100 ng, 250 ng, or 1 μg/site) and a negative control (Dulbecco PBSS or culture medium) on neutrophil chemotaxis were assessed after SC injection into the neck with an injectable biopolymer used as the vehicle. Tissue samples including the biopolymer plug were collected by biopsy at various time points from 3 hours to 7 days after injection. Neutrophil infiltration was evaluated by histologic scoring (experiments 1, 2, and 3) or flow cytometry (experiment 3). RESULTS Histologic neutrophil infiltration scores did not differ significantly among treatments at most evaluated time points. On flow cytometric analysis, log-transformed neutrophil counts in biopsy specimens were significantly greater for the ReqIL-8 treatment (1 μg/site) than the negative control treatment at 3 but not 6 hours after injection; results did not differ between ReqIL-4 and control treatments at either time point. Negative control treatments induced an inflammatory response in most equids in all experiments. CONCLUSIONS AND CLINICAL RELEVANCE Flow cytometry was a more reliable method to estimate neutrophil migration than histologic score analysis. The ReqIL-4 treatment did not induce a detectable neutrophil response, compared with the negative control treatment in this study. Evidence of inflammation in negative control samples suggested the biopolymer is not a suitable vehicle for use in equids.

Objective-To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species. Animals-5 clinically normal horses and 5 clinically normal donkeys. Procedures-Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables. Results-In horses and donkeys, mean +/- SD area under the curve was 18.8 +/- 7.31 microgram/mL/h and 4.6 +/- 2.55 microgram/mL/h, respectively; mean residence time (MRT) was 9.6 +/- 9.24 hours and 0.6 +/- 0.36 hours, respectively. Total body clearance (CL(T)) was 34.7 +/- 9.21 mL/kg/h in horses and 187.9 +/- 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VD(SS)) was 270 +/- 160.5 mL/kg in horses and 93.2 +/- 33.74 mL/kg in donkeys. All values, except VD(SS), were significantly different between donkeys and horses. Conclusions and Clinical Relevance-The small VD(SS) of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CL(T) for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CL(T) of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.

Paired metacarpi obtained at necropsy from 100 horses ranging in age from term fetus to 35 years were examined to estimate the prevalence and sites of metacarpal fusion. Metacarpal fusion was seen in 192 of 200 metacarpi, and 78% of all horses 2 years or older had 2 or more fusions. Fusion of the second metacarpal bone to the third metacarpal bone was significantly (P < 0.001) more common than was fusion of the fourth to the third metacarpal bone. Fusions appeared for the most part in pairs and were bilaterally symmetric. Rooney-Prickett type-A carpometacarpal joint configurations (in which there is no measurable articulation between the third carpal and second metacarpal bones) were rare in this population, and Rooney-Prickett type-B configurations (in which there is a measurable articulation between the third carpal and second metacarpal bones) were observed in 98.5% of metacarpi. Medial metacarpal fusion was positively correlated with age, occupation, and proportion of the proximal projection of the carpometacarpal distal joint surface that was taken by the second metacarpal bone. Lateral metacarpal fusion was positively correlated with age and the proportion of the proximal projection of the carpometacarpal distal joint surface taken by the fourth metacarpal bone. Horses in performance careers (racing, race training, or show ring occupations) had an earlier development of the first 2 fusions than did horses in other or unknown occupations; development of the third and fourth fusions were not significantly different between occupation groups. The rate of metacarpal fusion per horse-year appeared to be at least 10 times higher than a clinically evident rate.

OBJECTIVE To investigate the effects of orally administered trazodone on intraocular pressure (IOP), pupil diameter measured in the vertical plane (ie, vertical pupil diameter [VPD]), selected physical examination variables, and sedation level in healthy equids. ANIMALS 7 horses and 1 pony. PROCEDURES Food was withheld for 12 hours prior to drug administration. After baseline (time 0) sedation scoring, physical examination, and measurement of IOP and VPD, equids received 1 dose (approx 6 mg/kg) of trazodone orally. Examination and measurement procedures were repeated 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Blood samples were collected at each time point for analysis of plasma trazodone concentrations. Repeated-measures analysis was used to compare examination results between downstream time points and baseline. RESULTS 7 of 8 equids had mild sedation from 0.5 to 8 hours after treatment; compared with baseline values, mean IOP was significantly lower from 0.5 hours to 8 hours, mean VPD was significantly smaller at 0.5 hours, and mean rectal temperature was significantly lower from 1 to 8 hours after drug administration. Adverse effects (signs of excitement in 1 equid and sweating in 4) were self-limiting and considered minor. Mean maximum plasma concentration of trazodone was 1,493 ng/mL 0.75 hours after administration, and terminal half-life of the drug was 9.96 hours. CONCLUSIONS AND CLINICAL RELEVANCE The described oral dose of trazadone elicited sedation with a few self-limiting adverse effects in the study sample. Drug effects on IOP and VPD may alter ocular examination findings. Further investigation is warranted prior to use of trazodone for sedation in equids, particularly those with ophthalmic conditions.

Bacampicillin hydrochloride is an ester prodrug that is hydrolyzed to ampicillin after its absorption from the gastrointestinal tract. It was administered intragastrically at a dose rate of 13.5 mg/kg of body weight to ponies and horses, and was highly bioavailable (F = 41.0%), compared with other penicillins in adult horses. The high peak ampicillin plasma concentration of 6.1 +/- 0.5 micrograms/ml achieved and persistence of the antibiotic at concentration of 0.3 +/- 0.1 micrograms/ml 6 hours after its intragastric administration, suggest that bacampicillin hydrochloride may reach suitable bactericidal concentrations for treatment of infections caused by susceptible microorganisms. In a separate experiment, dichlorvos, an organophosphate compound that inhibits some of the esterase activity in plasma, was administered orally to the same animals at a dose rate of 40 mg/kg followed by intragastric administration of bacampicillin hydrochloride at a dose of 13.5 mg/kg. Plasma pseudocholinesterase and erythrocyte acetylcholinesterase activities were reduced to < 5% of reference (predichlorvos) values after dichlorvos administration. However, rate of hydrolysis of bacampicillin into ampicillin was not affected. Consequently, the disposition and fate of bacampicillin when administered intragastrically 1 day after dichlorvos administration were similar to the values obtained after administration of bacampicillin alone. Intragastric coadministration of probenecid at a dose rate of 75 mg/kg and bacampicillin at 13.5 mg/kg limited absorption of the antibiotic from the gastrointestinal tract. This suggests existence of a common transport mechanism for bacampicillin and probenecid in the gastrointestinal wall, and precludes use of this combination for treatment. The bioavailable fraction of ampicillin after combination treatment indicated prolonged residence time in the plasma, presumably as a consequence of reduced renal tubular secretion.

Solução hipertônica de cloreto de sódio a 7,5% tem sido utilizada no tratamento do choque hipovolêmico. Sua ação é caracterizada pelo aumento do débito cardíaco, da pressão arterial sistêmica e do volume plasmático. O objetivo deste estudo foi avaliar a ação da solução hipertônica de cloreto de sódio a 7,5% (4 ml/kg) no tratamento da hipotensão arterial induzida pela anestesia geral com halotano em eqüinos. Foram utilizados 15 eqüinos adultos, de ambos os sexos e raças e pesos variados, encaminhados a processos cirúrgicos eletivos. A técnica anestésica constituiu-se de sedação com detomidina, indução anestésica com éter gliceril guaiacol, midazolam e quetamina e manutenção anestésica com halotano em oxigênio. Estabeleceu-se como valor mínimo para infusão de solução hipertônica de cloreto de sódio a 7,5%, pressão arterial média inferior a 60 mmHg. Foram avaliados os seguintes parâmetros: freqüência e ritmo cardíacos; pressão arterial sistólica, diastólica e média; freqüência respiratória; tempo de preenchimento capilar; gases sangüíneos, pH arterial, bicarbonato plasmático; saturação da oxi-hemoglobina; concentração plasmática de sódio e cloreto e hematócrito. Considerou-se o tempo zero como controle e os parâmetros foram aferidos aos 5, 15, 30 e 60 minutos após a infusão. Verificou-se aumento significativo dos valores da pressão arterial, a qual manteve-se elevada durante o período de observação. Os valores do hematócrito diminuíram significativamente demonstrando ter havido expansão volêmica. Houve discreta hipernatremia e hipercloremia. Os demais parâmetros permaneceram inalterados. Pode-se concluir que a solução hipertônica de cloreto de sódio a 7,5% mostrou-se efetiva, podendo ser utilizada com segurança nos processos hipotensivos desencadeados pela anestesia geral com halotano.