Urinary tract infections are commonly encountered in domestic animals, and among the most common causes is E coli. Guidelines for the treatment of UTIs recommended culture and susceptibility to determine the antibiotic with the lowest global priority that is able to effectively treat the infection. Amoxicillin‐clavulanate is among the most commonly used antibiotics in the treatment of urinary tract infections, as it is relatively broad spectrum, generally effective against E coli, and readily available. However, current CLSI (the organization that sets laboratory standards) guidelines for amoxicillin-clavulanate in cats use plasma concentrations as a breakpoint, when it is known the drug concentrates in the urine.
The purpose of this paper was to measure the concentrations of amoxicillin-clavulanate in feline urine after oral administration in order to update CLSI guidelines. The study was designed as a prospective trial measuring urine drug concentrations in clinically healthy cats.
Twelve healthy cats were recruited from a colony. Eleven cats were neutered males and one was a spayed female. Cats had standard CBC/Biochemistry/Urinalysis testing performed to ensure health prior to enrollment. Cats were maintained on a standard kibble diet with free water and trained to urinate in non-absorbent cat litter. After acclimation, each cat was administered amoxicillin‐clavulanate 62.5mg every 12 hours for three consecutive doses (a standard dose and frequency for an average sized cat).
Urine samples were collected after each dose. After the third dose, three urine samples were collected 2 hours apart. For cats who did not voluntarily urinate a sedated cystocentesis sample was collected. Cats were adopted out after this study. One cat was excluded form analysis as he had not voided manually at all by the conclusion of the study.
Urine concentrations of amoxicillin and clavulanic acid were measured after this study. Based on the concentrations, pharmacokinetic data was calculated. Amoxicillin was determined to have a terminal half-life of 1.99 hours, and clavulanic acid of 2.17 hours.
Approximately 30% of administered amoxicillin was recovered (slightly lower than expected for a beta-lactam). The concentration of amoxicillin in urine remained above the MIC for wild-type E coli (8ug/mL) for 100% of the dosing interval in the study. As amoxicillin is considered a time-dependant antibiotic, this suggests that usual doses of oral amoxicillin reach a urinary concentration well above the traditional plasma MIC (0.25ug/mL).
There were several limitations to this study. Testing was done in healthy cats, however UTIs may be more common in cats with renal disease or other causes of dilute urine, and other data has shown lower urinary concentrations of amoxicillin‐clavulanate in cats with CKD. Sample sizes were small, however adequate for a study of this type.
The data presented in this study suggests that current CLSI guidelines may need to be updated, and that a large number of E coli UTIs declared “resistant” to amoxicillin‐clavulanate with current guidelines may actually be susceptible. This may allow increased use of amoxicillin‐clavulanate and reservation of higher tier antibiotics for truly resistant pathogens. (MRK)
Weese JS, Blondeau J, Boothe D, et al. International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Vet J. 2019; 247: 8‐ 25.