Robert Goggs

Objective: To determine the effect of a clinically relevant dose of trazodone on platelet count and function in healthy horses. Study design: Prospective, controlled, cross‐over study. Animals: Ten healthy horses. Methods: Horses were administered either 7 mg/kg trazodone orally in corn syrup or an equal amount of corn syrup (control), every 12 h for 2 weeks. After 2 weeks, horses underwent at least a 2‐week washout period before being administered the alternate treatment (trazodone or control). Blood was collected before the first treatment administration (day 0) and after 2 weeks of treatment for each phase of the study. Complete blood cell counts, platelet function assays, and plasma trazodone concentrations were assessed. Data were analyzed using repeated measures ANOVA with significance set at p < .05. Results: No differences in platelet count or tests of platelet function were observed at any time point after trazodone or control treatment. There were no adverse effects of trazodone administration appreciated on repeat physical examinations or daily ataxia scoring. Conclusions: No inhibitory effects of trazodone on platelet function in horses were detected. Clinical significance: This study suggests administration of oral trazodone at 7 mg/kg prior to surgery is unlikely to impair platelet function in healthy horses.

Objective: To estimate the prevalence of Campylobacter jejuni infection among apparently healthy dogs versus dogs with acute diarrhea in central New York, identify risk factors for infection among dogs, and characterize the isolates to evaluate potential risk to public health. Methods: In this prospective study, fecal samples were collected from dogs from January 2022 through September 2023. Exposure data on each dog were obtained via client questionnaire. Real-time PCR was used to detect C jejuni , and positive samples were subjected to bacteriologic culture. Isolate characterization via antimicrobial susceptibility testing and whole-genome sequencing was performed. Results: A total of 212 dogs were included. The prevalence of fecal C jejuni shedding as detected by PCR did not differ significantly between healthy dogs and dogs with acute diarrhea. Campylobacter jejuni PCR-positive status was more common among puppies (14.3%) than adults (2.8%), and it was more common among dogs that had recently consumed table scraps or trash (9.6%) versus dogs without that history (2.0%). Conclusions: A history of acute diarrhea was not significantly associated with C jejuni PCR-positive status, although the relatively small number of dogs with diarrhea precluded a robust comparison to healthy dogs. Clinical Relevance: Campylobacter jejuni was identified in healthy dogs and dogs with acute diarrhea, underscoring the potential for zoonotic transmission. Puppies and cases with a history of consuming table scraps or food waste may be at increased risk.

Objective: To assess the feasibility of gene expression profiling of platelets in dogs with sepsis. Methods: This was a prospective observational feasibility study conducted at a university veterinary teaching hospital. All study dogs had CBCs and serum biochemistry profiles, and blood samples were collected for platelet isolation. Gene expression profiling of isolated platelets was performed using a commercial multiplex assay based on direct hybridization and detection of single RNA molecules bar coded with fluorescent probes. Quality control, normalization, and data visualization were performed using standardized workflows. Raw counts were exported, and differential expression between groups was assessed. Results: 6 client-owned dogs with sepsis and 6 healthy dogs were enrolled from March through August 2023. Platelet isolation and transcript profiling were successful for all dogs. The septic dog group included 3 males and 3 females with peritonitis (n = 3), pyometra (n = 2), and pyothorax. Principal component analysis did not fully segregate septic from healthy dogs, but disease status accounted for 59% of the variance. Upregulated genes contributing substantially to principal component analysis variance included those for S100 calcium-binding proteins (S100s) and cytokines. Significantly upregulated genes based on log ₂ fold change included S100A8, S100A12, cathelicidin, lactoferrin, and innate immune response signaling proteins. Conclusions: Sample processing and data analysis workflows are scalable to larger, confirmatory studies to explore potential sepsis biomarkers. Clinical Relevance: Platelet gene expression profiles might offer insights into sepsis pathophysiology and potential diagnostic and prognostic biomarkers. Follow-up studies are warranted to characterize platelet expression profiles in larger populations of dogs with sepsis and noninfectious critical illnesses.

Achieving therapeutic plasma concentrations is essential for effective antimicrobial drug (AMD) treatment. Critical illness alters drug distribution and clearance, potentially impacting AMD effectiveness. We conducted a prospective observational study in 25 critically ill dogs to evaluate the pharmacokinetics (PK) of intravenous (IV) ampicillin/sulbactam and achievement of the efficacy target of ≥ 50% of the dosing interval with unbound plasma drug concentrations above the minimum inhibitory concentration ( f T > MIC). All dogs received IV ampicillin/sulbactam from a commercial formulation at a dosage of 20 mg/kg ampicillin/10 mg/kg sulbactam. Plasma concentrations were measured using liquid chromatography–mass spectrometry. PK modeling determined best‐fit compartmental models, and Monte Carlo simulations evaluated the probability of target attainment for bacterial MICs. A one‐compartment model best described ampicillin PK, while a two‐compartment model fit sulbactam. Monte Carlo simulations indicated a 90% probability that ampicillin at 20 mg/kg IV q8 h would achieve the Clinical and Laboratory Standards Institute (CLSI) veterinary breakpoint of 0.25 μg/mL for > 50% of the dosing interval. There was only a 10% probability of achieving the human breakpoint of 8 μg/mL. At 0.25 μg/mL, most Enterobacterales isolates would be resistant. The ampicillin/sulbactam dosage tested meets veterinary CLSI standards for ampicillin but might not effectively treat Enterobacterales infections in critically ill dogs.

Introduction: Immune-mediated hemolytic anemia (IMHA) is an important immunologic disorder in dogs that is associated with high mortality rates, frequently due to thromboembolism. Multiple factors contribute to the pathophysiology of thrombosis in IMHA including intravascular tissue factor expression, platelet activation, and neutrophil extracellular trap (NET) formation. It was hypothesized that dogs with IMHA have impaired fibrinolysis that can be detected using a modified viscoelastic assay and that biomarkers of NET formation are associated with this hypofibrinolysis.Methods: Twenty dogs with non-associative IMHA were enrolled and paired thromboelastography (TEG) assays with and without additional tissue plasminogen activator (tPA) performed. A panel of hemostasis tests including measurement of plasma thrombin-activatable fibrinolysis inhibitor (TAFI) activity, active plasminogen activator inhibitor-1 (PAI-1), and concentrations of cell-free DNA (cfDNA) and nucleosomes were also performed.Results: Dogs with IMHA had hypercoagulable TEG tracings, increased TAFI activity and frequently displayed fibrinolysis resistance defined as minimal lysis in tPA augmented TEG assays. Increased concentrations of cfDNA, nucleosomes and active PAI-1 in dogs with IMHA compared to healthy controls were identified.Discussion: These observations support the hypothesis that hypofibrinolysis is a common feature of IMHA in dogs. Increased plasma active PAI-1 concentrations and TAFI activities might contribute to the observed hypofibrinolysis. The combined hypercoagulability and hypofibrinolysis observed supports recent recommendations to provide thromboprophylaxis to all dogs with IMHA. These findings also suggest that NETosis might contribute to the common prothrombotic imbalance of IMHA in dogs.

The fluoroquinolones, particularly enrofloxacin, are frequently used to treat life‐threatening bacterial infections in small animal emergency and critical care practice. Achieving therapeutic plasma concentrations is essential for effective treatment, whereas inadequate concentrations select for resistance among Enterobacterales and Pseudomonas aeruginosa . We conducted a prospective observational study in 19 critically ill dogs to evaluate the pharmacokinetics (PK) of enrofloxacin and its active metabolite ciprofloxacin after administration of a standardized dosage (10 mg/kg IV q24 h). Plasma concentrations were measured at multiple time points using liquid chromatography‐mass spectrometry, and PK modeling was performed to determine best‐fit compartmental models. A 2‐compartment model best described enrofloxacin PK. There was considerable between‐dog variation in PK parameters, likely due to known challenges of drug dosing in critical illness. The percentage conversion of enrofloxacin to ciprofloxacin was lower than has previously been reported in healthy dogs. Pharmacodynamic analyses suggest that enrofloxacin administered at 10 mg/kg IV q24 h to critically ill dogs will likely result in effective treatment of infections by susceptible and susceptible dose‐dependent bacteria, and achieved concentrations may be sufficient to reduce the risk of AMR development.

Introduction: Hemostatic imbalance in dogs with sepsis is characterized by hypercoagulability and hypofibrinolysis. We aimed to determine whether these abnormalities are unique features of sepsis or are also present in dogs with non-septic critical illness. Secondary aims were to assess relationships between coagulation assay results and circulating markers of neutrophil extracellular traps (NETs), and to relate coagulation assay abnormalities with survival in dogs with sepsis.Methods: This prospective single-center observational cohort study enrolled 55 client-owned dogs that satisfied at least 2 systemic inflammatory response syndrome (SIRS) criteria. Dogs with a bacterial infection were categorized as sepsis, those without evidence of infection were categorized as non-infectious systemic inflammation (nSIRS). Clotting times, fibrinogen and D-dimer concentrations, and activities of antithrombin (AT), antiplasmin (AP), thrombin activatable fibrinolysis inhibitor (TAFI), and total and active plasminogen activator inhibitor-1 (PAI-1) were measured. Thrombin generation and overall hemostasis potential assays were performed and concentrations of cell-free DNA (cfDNA) and H3.1 nucleosomes quantitated.Results: Compared to dogs with nSIRS, dogs with sepsis had higher fibrinogen concentrations, greater endogenous thrombin potential, higher AP and TAFI activities and greater overall hemostasis and coagulation potential values. H3.1 nucleosome and cfDNA concentrations were strongly correlated and significantly associated with various coagulation variables. In dogs with sepsis, non-survivors had lower AT activity, and higher active PAI-1 and H3.1 nucleosome concentrations.Discussion: Relative to non-septic critically ill dogs, dogs with sepsis are hyperfibrinogenemic, hypercoagulable and have higher AP and TAFI activities. Concentrations of H3.1 nucleosomes and active PAI-1 and AT activity might have prognostic value in dogs with sepsis.