An Evaluation of the Impact of an OPEN Stewardship Generated Feedback Intervention on Antibiotic Prescribing among Primary Care Veterinarians in Canada and Israel.

An interrupted time-series study design was implemented to evaluate the impact of antibiotic stewardship interventions on antibiotic prescribing among veterinarians. A total of 41 veterinarians were enrolled in Canada and Israel and their prescribing data between 2019 and 2021 were obtained. As an intervention, veterinarians periodically received three feedback reports comprising feedback on the participants' antibiotic prescribing and prescribing guidelines. A change in the level and trend of antibiotic prescribing after the administration of the intervention was compared using a multi-level generalized linear mixed-effect negative-binomial model. After the receipt of the first (incidence rate ratios [IRR] = 0.88; 95% confidence interval (CI): 0.79, 0.98), and second (IRR = 0.85; 95% CI: 0.75, 0.97) feedback reports, there was a reduced prescribing rate of total antibiotic when other parameters were held constant. This decline was more pronounced among Israeli veterinarians compared to Canadian veterinarians. When other parameters were held constant, the prescribing of critical antibiotics by Canadian veterinarians decreased by a factor of 0.39 compared to that of Israeli veterinarians. Evidently, antibiotic stewardship interventions can improve antibiotic prescribing in a veterinary setting. The strategy to sustain the effect of feedback reports and the determinants of differences between the two cohorts should be further explored.

Fecal Microbiome Features Associated with Extended-Spectrum ß-Lactamase-Producing Enterobacterales Carriage in Dairy Heifers.

Extended-spectrum ß-lactamases (ESBLs) are a growing public health threat, and one key human exposure point is through livestock and the food supply. Understanding microbiome factors associated with fecal ESBL carriage can help detect and ideally assist with controlling and preventing ESBL dissemination among livestock. The objective of this study was to investigate the diversity and composition of the heifer fecal microbiota in ESBL-producing Enterobacterales (ESBL-PE) carriers and noncarriers. A total of 59 fecal samples were collected from replacement heifers between 12 and 18 months old from eight dairy farms in central Israel. Genomic DNA was extracted, and 16S rRNA amplicon sequencing was performed (Illumina short reads), focusing on a comparison between 33 ESBL-PE carriers (55.9%) and 26 (44.1%) noncarriers. Samples were analyzed and compared using QIIME2 (DADA2 pipeline and taxonomic assignment with SILVA database) and associated R packages for alpha and beta diversity and taxonomic abundances. Alpha diversity (Shannon diversity) and beta diversity (unweighted UniFrac) showed no significant difference between ESBL-PE carriers and noncarriers. Heifers from farms feeding calves with pooled colostrum had higher ESBL-PE carriage rates than heifers from farms feeding with individual mother colostrum (p < 0.001). Taxonomical abundance analysis revealed that the most common bacterial phyla were Bacteroidetes (44%) and Firmicutes (38%). There was no significant difference in taxonomic composition between ESBL-PE carriers and noncarriers at the phylum and genus levels. However, LEfSe biomarker discovery analysis identified several genera which were significantly different between carriers and noncarriers. For example, Prevotellacaea, Bacteroides, Rikenellaceae, and uncultured Bacteroidales were more abundant in ESBL carriers than noncarriers. Some aspects of microbiota composition differ between ESBL carriers and noncarriers in dairy heifers, specifically the abundance of certain genera. Feeding with pooled colostrum may play a role in that assembly. These could potentially serve as markers of ESBL-PE carriage. However, further research is needed to determine whether these observed differences have a significant impact on colonization with ESBL-PE.

Evaluation of an OPEN Stewardship generated feedback intervention to improve antibiotic prescribing among primary care veterinarians in Ontario, Canada and Israel: protocol for evaluating usability and an interrupted time-series analysis.

INTRODUCTION: Antimicrobial resistance (AMR) impacts the health and well-being of animals, affects animal owners both socially and economically, and contributes to AMR at the human and environmental interface. The overuse and/or inappropriate use of antibiotics in animals has been identified as one of the most important drivers of the development of AMR in animals. Effective antibiotic stewardship interventions such as feedback can be adopted in veterinary practices to improve antibiotic prescribing. However, the provision of dedicated financial and technical resources to implement such systems are challenging. The newly developed web-based Online Platform for Expanding Antibiotic Stewardship (OPEN Stewardship) platform aims to automate the generation of feedback reports and facilitate wider adoption of antibiotic stewardship. This paper describes a protocol to evaluate the usability and usefulness of a feedback intervention among veterinarians and assess its impact on individual antibiotic prescribing. METHODS AND ANALYSIS: Approximately 80 veterinarians from Ontario, Canada and 60 veterinarians from Israel will be voluntarily enrolled in a controlled interrupted time-series study and their monthly antibiotic prescribing data accessed. The study intervention consists of targeted feedback reports generated using the OPEN Stewardship platform. After a 3-month preintervention period, a cohort of veterinarians (treatment cohort, n=120) will receive three feedback reports over the course of 6 months while the remainder of the veterinarians (n=20) will be the control cohort. A survey will be administered among the treatment cohort after each feedback cycle to assess the usability and usefulness of various elements of the feedback report. A multilevel negative-binomial regression analysis of the preintervention and postintervention antibiotic prescribing of the treatment cohort will be performed to evaluate the impact of the intervention. ETHICS AND DISSEMINATION: Research ethics board approval was obtained at each participating site prior to the recruitment of the veterinarians. The study findings will be disseminated through open-access scientific publications, stakeholder networks and national/international meetings.

Extended-Spectrum ß-Lactamase-Producing Enterobacterales Shedding by Dogs and Cats Hospitalized in an Emergency and Critical Care Department of a Veterinary Teaching Hospital.

Extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) gut shedding in human medicine is considered as a major reservoir for ESBL-associated infections in high risk patients. In veterinary medicine, data regarding ESBL-PE gut shedding on admission to emergency and critical care department is scarce. We aimed to determine ESBL-PE shedding rates by dogs and cats in this setting and to determine the risk factors for shedding, at two separate periods, three-years apart. Rectal swabs were collected from animals, on admission and 72 h post admission, enriched and plated on Chromagar ESBL plates, followed by bacterial identification. ESBL phenotype was confirmed and antibiotic susceptibility profiles were determined (Vitek 2). Medical records were reviewed for risk factor analysis (SPSS). Overall, 248 animals were sampled, including 108 animals on period I (2015-2016) and 140 animals on period II (2019). In both periods combined, 21.4% of animals shed ESBL-PE on admission, and shedding rates increased significantly during hospitalization (53.7%, p-value < 0.001). The main ESBL-PE species were Escherichia coli and Klebsiella pneumoniae, accounting for more than 85% of the isolates. In a multivariable analysis, previous hospitalization was a risk factor for ESBL-PE gut shedding (p-value = 0.01, Odds ratio = 3.05, 95% Confidence interval 1.28-7.27). Our findings demonstrate significant ESBL-PE gut shedding among small animals in the emergency and critical care department, posing the necessity to design and implement control measures to prevent transmission and optimize antibiotic therapy in this setting.

Effects of fenoldopam on kidney function parameters and its therapeutic efficacy in the management of acute kidney injury in dogs with heatstroke.

BACKGROUND: Acute kidney injury (AKI) is common in dogs, but evidence of efficacy of its treatment is lacking. OBJECTIVE: To evaluate the efficacy of fenoldopam in the management of AKI. ANIMALS: Forty dogs with naturally occurring heatstroke. METHODS: Dogs were prospectively enrolled and divided into treatment and the placebo groups (fenoldopam, constant rate infusion [CRI] of 0.1 µg/kg/min or saline, respectively). Urine production (UP) was measured using a closed system. Urinary clearances were performed at 4, 12, and 24 hours after presentation to estimate the effect of fenoldopam on UP, glomerular filtration rate (GFR) and sodium fractional excretion (NaFE). RESULTS: At presentation, severity of heatstroke, based on a previously developed scoring system, was similar between the study groups, but was significantly worse in nonsurvivors compared with survivors. Fenoldopam administration was not associated with hypotension. Overt AKI was diagnosed, based on the International Renal Interest Society guidelines in 22/40 (55%) of the dogs. Overall, 14/40 dogs (35%) died, with no significant (P = .507) mortality rate difference between the fenoldopam (6/20 dogs; 30%) and placebo (8/20; 40%) groups. The proportion of dogs with AKI did not differ between the fenoldopam and the placebo groups (9/20; 45% versus 13/20; 65%, respectively; P = .204). There were no differences in UP, GFR, and NaFE between the fenoldopam and the placebo groups. CONCLUSION AND CLINICAL IMPORTANCE: Fenoldopam CRI at 0.1 µg/kg/min did not have a clinically relevant effect on kidney function parameters in dogs with severe heatstroke-associated AKI.

Hemostatic abnormalities in dogs with naturally occurring heatstroke.

OBJECTIVE: To investigate hemostatic analyte abnormalities and their association with mortality in dogs with naturally occurring heatstroke. DESIGN: Prospective observational study. SETTING: University teaching hospital. ANIMALS: Thirty client-owned dogs with naturally occurring heatstroke. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Citrated and EDTA blood samples were collected at presentation and at 4, 12, 24, 36, and 48 hours postpresentation (PP). Hemostatic tests performed included platelet count, prothrombin and activated partial thromboplastin times (PT and aPTT, respectively), antithrombin activity (ATA), total protein C activity (tPCA), fibrinogen, and D-dimer concentrations. The overall survival rate was 60% (18/30 dogs). Older age, higher heart rate and rectal temperature at presentation, and time from onset of clinical signs to presentation were significantly associated with mortality. Hemostatic analytes at presentation were not associated with mortality. Prolonged PT and aPTT at 12-24 hours PP, lower tPCA at 12 hours PP, and hypofibrinogenemia at 24 hours PP were significantly (P < 0.05) associated with mortality. Increased D-dimer concentration and low ATA were common at all time points, but were not associated with mortality. The frequency of disseminated intravascular coagulation (DIC) increased in nonsurvivors throughout hospitalization, but the development of DIC was not associated with mortality. The number of abnormal coagulation disturbances during the first 24 hours was significantly higher in nonsurvivors (P = 0.04). CONCLUSIONS: Hemostatic derangements are common in dogs with naturally occurring heatstroke. Alterations in PT, aPTT, tPCA, and fibrinogen concentrations appear to be associated with the outcome at 12-24 hours PP, exemplifying the need for serial measurement of multiple laboratory hemostatic tests during hospitalization, even when within reference interval on presentation. The development of DIC, as defined in this cohort, was not associated with mortality; however, nonsurvivors had significantly more coagulation abnormalities during the first 24 hours PP.