Effect of institutional antimicrobial stewardship guidelines on prescription of critically important antimicrobials for dogs and cats.

BACKGROUND: Veterinary hospital antimicrobial stewardship (AMS) guidelines might help combat antimicrobial resistance (AMR). OBJECTIVES: Determine the conditions and types of infection for which antimicrobial drugs (AMDs) deemed critically important (CIA) by the World Health Organization (WHO) were prescribed and assess the effect of hospital AMS guidelines on adherence to International Society for Companion Animal Infectious Diseases published guidelines for the treatment of superficial bacterial folliculitis, respiratory tract disease and urinary tract infection in these cases. ANIMALS: Dogs and cats managed at an academic veterinary hospital from 1/21 to 6/21 and 9/21 to 6/22. METHODS: Prescriptions of cephalosporins (third or fourth generation), glycopeptides, macrolides/ketolides, polymyxins, and quinolones were identified. Data on culture and susceptibility (C/S) testing and previous AMD exposure were collected. Frequencies were compared between time periods using Fisher's exact test with Bonferroni corrections. RESULTS: In animals prescribed ≥1 WHO-CIA AMD, fluoroquinolones were the most frequently prescribed WHO-CIA class in dogs (567/1724, 32.9%) and cats (192/450, 42.7%). No animals were prescribed carbapenems, dihydrofolate reductase inhibitors/sulfonamides, or polymyxins. No cats were prescribed aminoglycosides or amphenicols. Institutional guidelines were followed in 57.8% (324/561) cases. The most frequent causes of nonadherence were failure to perform C/S testing 46.0% (109/237) and unnecessary use of a higher-tier AMD 43.0% (102/237). Bacterial C/S testing was more frequently performed after AMS guideline institution (59.7% vs. 46.8%, P = 0.0006). CONCLUSIONS AND CLINICAL IMPORTANCE: Adherence to published guidelines remained poor despite an increase in C/S testing. There were no changes in the frequencies of confirmed infections, positive cultures or AMD resistance between time periods.

Identifying potential biomarkers and therapeutic targets for dogs with sepsis using metabolomics and lipidomics analyses.

Sepsis is a diagnostic and therapeutic challenge and is associated with morbidity and a high risk of death. Metabolomic and lipidomic profiling in sepsis can identify alterations in metabolism and might provide useful insights into the dysregulated host response to infection, but investigations in dogs are limited. We aimed to use untargeted metabolomics and lipidomics to characterize metabolic pathways in dogs with sepsis to identify therapeutic targets and potential diagnostic and prognostic biomarkers. In this prospective observational cohort study, we examined the plasma metabolomes and lipidomes of 20 healthy control dogs and compared them with those of 21 client-owned dogs with sepsis. Patient data including signalment, physical exam findings, clinicopathologic data and clinical outcome were recorded. Metabolites were identified using an untargeted mass spectrometry approach and pathway analysis identified multiple enriched metabolic pathways including pyruvaldehyde degradation; ketone body metabolism; the glucose-alanine cycle; vitamin-K metabolism; arginine and betaine metabolism; the biosynthesis of various amino acid classes including the aromatic amino acids; branched chain amino acids; and metabolism of glutamine/glutamate and the glycerophospholipid phosphatidylethanolamine. Metabolites were identified with high discriminant abilities between groups which could serve as potential biomarkers of sepsis including 13,14-Dihydro-15-keto Prostaglandin A2; 12(13)-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid); and 9-HpODE (9-Hydroxyoctadecadienoic acid). Metabolites with higher abundance in samples from nonsurvivors than survivors included 3-(2-hydroxyethyl) indole, indoxyl sulfate and xanthurenic acid. Untargeted lipidomic profiling revealed multiple sphingomyelin species (SM(d34:0)+H; SM(d36:0)+H; SM(d34:0)+HCOO; and SM(d34:1D3)+HCOO); lysophosphatidylcholine molecules (LPC(18:2)+H) and lipophosphoserine molecules (LPS(20:4)+H) that were discriminating for dogs with sepsis. These biomarkers could aid in the diagnosis of dogs with sepsis, provide prognostic information, or act as potential therapeutic targets.