Divergent veterinarian and cat owner perspectives are barriers to reducing the use of cefovecin in cats.

OBJECTIVE: To understand veterinarian and cat owner perspectives on antimicrobial use in cats, reasons for prescribing cefovecin, and barriers to improving antimicrobial stewardship, including veterinarian and cat owner perspectives of giving oral medication to cats. SAMPLE: 21 New York veterinarians and 600 cat owners across the US. METHODS: Cat owners were surveyed about their preferences for and experiences in giving oral medications to cats and their experiences with antimicrobials specifically. Veterinarians were interviewed about antimicrobial use decisions in cats, benefits and drawbacks of cefovecin, and their perspectives on antimicrobial resistance. RESULTS: Many veterinarians reported feeling pressure to prescribe antimicrobials, while 41% of cat owners reported requesting antimicrobials. Although veterinarians are aware of the downsides of prescribing cefovecin, many prescribed cefovecin in situations where an antimicrobial was not needed or cefovecin may not have been the best choice. Veterinarians thought that 20% of cat owners could not give oral medications, but < 10% of cat owners had a cat that was impossible to medicate. CLINICAL RELEVANCE: The disconnect between veterinarians' assessment of and cat owners' reported abilities in administering oral medication may contribute to cefovecin use. Demonstrating for cat owners how to give oral medication may help improve compliance and reduce the use of parenteral long-acting formulations. Structural and educational interventions are needed to address other contributors to inappropriate antimicrobial use. This research provides the specific considerations about barriers and motivations for cat owners and veterinarians that are required to guide strategic, tailored interventions for both audiences to advance stewardship.

Pathways to sustainable antimicrobial use in cats.

Antimicrobial stewardship encompasses all the individual and collective actions that medical professionals take to preserve the efficacy of antimicrobials. It is a one-health problem, affecting animals and humans. The current state of antimicrobial use in cats, particularly (1) the overuse and improper use of cefovecin, which belongs to the third-generation cephalosporin class that is critically important to human health, and (2) use of antimicrobials when they are not needed, poses unsustainable risks of antimicrobial resistance. This paper describes the principles of antimicrobial stewardship and stewardship challenges faced by feline veterinarians, including (1) poor adherence to or awareness of antimicrobial use guidelines, (2) lack of access to affordable diagnostic tests and antibiograms, (3) lack of access to materials and tools for clients that may facilitate more sustainable antimicrobial use and help cat owners understand resistance risks, (4) underestimating the ability of cat owners to administer oral antimicrobials, and (5) limited time and resources to support stewardship efforts. Based on research described in this paper; an original research article by Cazer et al, JAVMA, December 2023; and a Currents in One Health article by Cobo-Angel et al, AJVR, December 2023, several solutions are proposed to advance antimicrobial stewardship in feline medicine. Many of these proposals were expressly requested by veterinarians interviewed in Cazer et al, JAVMA, December 2023. Education and training of veterinarians and cat owners is an essential step toward sustainable antimicrobial use, but it must be complemented with innovations in diagnostic testing, antimicrobial drug development, structural changes, and technological supports.

Cefovecin pharmacokinetics after single-dose intramuscular administration in cheetahs (Acinonyx jubatus).

Cefovecin is a third-generation cephalosporin with potential value for use in exotic felids due to its long duration of action. A sparse sampling protocol was implemented with 18 zoo-housed cheetahs (Acinonyx jubatus) to evaluate the pharmacokinetics of cefovecin (Convenia® ) after a single 8 mg/kg intramuscular injection. Blood was collected serially for 15 days following administration, and plasma cefovecin concentrations were determined using high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were estimated using population pharmacokinetic methods and non-linear mixed effects modeling (NLME). Cefovecin was well tolerated by all cats, with no adverse effects observed. Peak plasma cefovecin concentration was 84.75 µg/ml, with a mean residence time of 207.9 h and an elimination half-life of 144.1 h (6.00 days). Plasma concentrations of cefovecin were maintained >7 µg/ml in all individuals for the entire study duration (15 days). These concentrations are lower, and the half-life slightly shorter, than the values reported for domestic cats. Cefovecin was highly protein-bound (approximately 99.9%) in cheetah plasma, which is nearly identical to domestic cats. These results indicate that cefovecin is potentially useful as a long-acting antibiotic in cheetahs.

PHARMACOKINETIC PARAMETERS OF CEFOVECIN SODIUM (CONVENIA) IN CAPTIVE TIGERS ( PANTHERA TIGRIS).

A single 8 mg/kg dose of Cefovecin (Convenia®) was administered intramuscularly in the hindlimb of eight anesthetized captive tigers ( Panthera tigris) and serial blood samples were collected over the next 56 days to determine pharmacokinetic characteristics. High-performance liquid chromatography was utilized to determine plasma levels, and demonstrated a mean terminal half-life of 227.8 ± 29.3 hr. Cefovecin, >1 µg/ml, was detected in plasma levels up to 56 days postinjection. Protein binding of tiger plasma for cefovecin was 98%. The long duration of therapeutic plasma concentrations and lack of adverse effects make cefovecin a useful antimicrobial drug for tigers.

Evaluation of an outpatient protocol in the treatment of canine parvoviral enteritis.

OBJECTIVE: To compare 2 treatment protocols (standard in-hospital versus modified outpatient) in affecting the duration of treatment or survival of dogs with parvoviral enteritis. DESIGN: Prospective, randomized study. SETTING: University teaching hospital. ANIMALS: Client-owned dogs with naturally acquired parvovirus were randomized to receive either an inpatient (n = 20) or outpatient (n = 20) treatment protocol. INTERVENTIONS: Both groups received intravenous (IV) fluid resuscitation and correction of hypoglycemia at hospital admission. Following stabilization, basic inpatient interventions included administration of IV fluids, administration of cefoxitin (22 mg/kg IV q 8 h), and maropitant (1 mg/kg IV q 24 h). Basic outpatient interventions (provided in-hospital) included administration of subcutaneous (SC) fluid (30 mL/kg q 6 h), administration of maropitant (1 mg/kg SC q 24 h) and cefovecin (8 mg/kg SC once). Using daily electrolyte and glucose evaluations, dextrose and potassium supplementation was provided intravenously (inpatients) or orally (outpatients) as indicated. Rescue criteria were used in both groups for analgesia and nausea. All dogs were syringe fed a commercial canine convalescence diet (1 mL/kg PO q 6 h) until voluntary appetite returned. MEASUREMENTS AND MAIN RESULTS: Protocol success, defined as survival to hospital discharge, was 90% (18/20) for the inpatient group compared to 80% (16/20) for the outpatient group (P = 0.66). There was no difference detected in duration of hospitalization for inpatient dogs (4.6 ± 2 days) versus outpatient dogs (3.8 ± 1.8 days, P = 0.20). Metabolic disturbances were frequent in the outpatient group, with 50% of dogs requiring dextrose supplementation and 60% of dogs requiring potassium supplementation. CONCLUSIONS: An outpatient protocol may be a reasonable alternative for dogs that cannot receive standard in-hospital treatment for parvoviral enteritis. Diligent supportive care and monitoring are still required to optimize treatment of dogs with parvoviral enteritis in an outpatient setting.

Long-lasting concentrations of cefovecin after subcutaneous and intramuscular administration to Patagonian sea lions (Otaria flavescens).

Cefovecin is a third-generation cephalosporin developed as an aqueous solution for use by the subcutaneous route in dogs and cats. This study evaluated the duration of cefovecin plasma concentrations after single intramuscular (IM) or subcutaneous (SC) injection at different doses in 10 Patagonian sea lions (Otaria flavescens). Blood samples were collected serially from the day of the injection up to 60-90 days post-injection. Plasma drug concentrations were determined by high performance liquid chromatography-UV detection and pharmacokinetic parameters were calculated by non-compartmental analysis. No reactions or side effects associated with the drug were observed in any of the studied animals. Both routes showed very similar pharmacokinetic behaviour. Elimination half-life (11.3-21.6 days, SC; 13.1-15.9 days, IM) and mean residence time (17.6-36.8 days SC; 16.5-25.4 days IM) were, in all cases and doses, considerably longer than those previously reported for any other species. Based on these findings, and preliminary data on specific pathogen sensitivity, cefovecin was found to be a very promising antimicrobial for Patagonian sea lions, in particular those that are difficult to access or that are under certain rehabilitation conditions.

Bacterial species isolated from cats with lower urinary tract infection and their susceptibilities to cefovecin.

BACKGROUND: The aim of this study was to determine the bacterial species recovered from 61 cats with lower urinary tract infection (LUTI), and their susceptibility to cefovecin in vitro. RESULTS: The clinical signs and final clinical diagnosis for cats with confirmed LUTI were also reported. After physical examination of the cats, urine samples including ≥5-6 leucocytes in microscopic evaluation were cultured using bacteriological techniques. The isolates were identified by conventional microbiological methods and tested for in vitro susceptibility using the Kirby-Bauer disc diffusion method recommended by the Clinical Laboratory Standards Institute. Bacterial growth was observed in 16 of 61 urine samples. Antimicrobial susceptibility tests showed that 13 of 16 (81%) isolates were susceptible to cefovecin. The most frequently isolated bacterium from cats with signs of lower urinary tract infection, was Escherichia coli. CONCLUSION: Cefovecin was found to be effective in cats with LUTI. Because cefovecin is a new antimicrobial agent in veterinary medicine, there are only few studies about urine culture of cats with LUTI. It is the first study on in vitro activity of cefovecin against bacterial isolates from cats with lower urinary infections in Istanbul, Turkey.

In vitro interaction of some drug combinations to inhibit rapidly growing mycobacteria isolates from cats and dogs and these isolates' susceptibility to cefovecin and clofazimine.

OBJECTIVES: To investigate whether selected drug combinations used to treat rapidly growing mycobacteria (RGM) have drug-drug interactions that affect efficacy and to investigate each isolate's susceptibility to cefovecin and clofazimine, individually. DESIGN: In vitro susceptibility testing of bacterial isolates. METHODS: Initially, five feline isolates and one canine isolate from both Mycobacterium fortuitum and M. smegmatis clusters (n = 12) underwent microbroth susceptibility testing to individual drugs to establish minimum inhibitory concentrations (MIC) of cefovecin, ciprofloxacin, clarithromycin, clofazimine, doxycycline, enrofloxacin, trimethoprim and sulfanilamide (the latter two as a combination). Checkerboard assays were then performed for susceptible M. smegmatis isolates for the following combinations: clarithromycin (one isolate only) versus enrofloxacin, clarithromycin vs doxycycline, clarithromycin vs trimethoprim/sulfanilamide; enrofloxacin vs doxycycline (six isolates); enrofloxacin vs trimethoprim/sulfanilamide (six isolates). Susceptible M. fortuitum isolates were tested against enrofloxacin versus doxycycline (four isolates only). RESULTS: All six M. fortuitum isolates were susceptible to enrofloxacin, but only four of six were susceptible to doxycycline. All six M. smegmatis isolates were susceptible to doxycycline, enrofloxacin and trimethoprim/sulfanilamide. A single isolate from the 12, a M. smegmatis isolate, was susceptible to clarithromycin. The fractional inhibitory concentration of each drug ranged from 0.64 to 1.84, indicating that neither synergism nor antagonism was evident. All 12 isolates were resistant to cefovecin. The clofazimine MIC50 to inhibit isolate growth was approximately 3.3 µg/mL for both strains. CONCLUSION: Drugs commonly used for treatment of RGM, when tested as combinations, do not appear to antagonise one another in vitro. Cefovecin is not efficacious for treatment of RGM infections.

In vitro efficacy of cefovecin against anaerobic bacteria isolated from subgingival plaque of dogs and cats with periodontal disease.

Periodontal disease is a common disease of dogs and cats often requiring antimicrobial treatment as an adjunct to mechanical debridement. However, correct compliance with oral antimicrobial therapy in companion animals is often difficult. Cefovecin is a recently introduced veterinary cephalosporin that has demonstrated prolonged concentrations in extracellular fluid, allowing for dosing intervals of up to 14 days. Subgingival samples were collected from the oral cavity of 29 dogs and eight cats exhibiting grade 2 or grade 3 periodontal disease. Samples were cultivated on Wilkin Chalgrens agar and incubated in an anaerobic chamber for seven days. Selected anaerobic bacteria were isolated and identified to species level using 16S rRNA gene sequence analysis. Minimum inhibitory concentrations were determined for cefovecin and six additional antimicrobials using the agar dilution methodology recommended by the Clinical and Laboratory Standards Institute. The 65 clinical isolates were identified as Porphyromonas gulae (n = 45), Porphyromonas crevioricanis (n = 12), Porphyromonas macacae (n = 1), Porphyromonas cangingivalis (n = 1) Fusobacterium nucleatum (n = 2), Fusobacterium russii (n = 1) and Solobacterium moorei (n = 3). This is the first report of S. moorei being isolated from companion animals with periodontal disease. All isolates were highly susceptible to cefovecin, with a MIC90 of ≤0.125 µg/ml. Conversely, different resistance rates to ampicillin, amoxicillin and erythromycin between isolates were detected. Cefovecin is thus shown to be effective in vitro against anaerobic bacteria isolated from dogs and cats with periodontal disease.

Development of a method for the determination of cefovecin in plasma by HPLC.

A simple high-performance liquid chromatography method for the determination of cefovecin in small volume plasma has been developed. Following solid-phase extraction using Oasis HLB cartridges, samples were separated by reverse-phase high-performance liquid chromatography on an XBridge C8 (3.5 µm) 4.6 × 250 mm column and quantified using ultraviolet detection at 280 nm. The mobile phase was a mixture of 10 mm ammonium acetate (pH 3.5) and acetonitrile (89:11), with a flow rate of 0.85 mL/min. The standard curve ranged from 0.1 to 200 µg/mL. Intra- and Inter-assay variability for cefovecin was <10%, and the average recovery was >90%. The lower limit of quantitation was 0.1 µg/mL. This method was successfully applied to the analysis of cefovecin samples at our institution. This is also the first fully validated method with an internal standard that does not use mass spectrometry.