Evaluation of urine concentrations of amoxicillin and clavulanate in cats

BACKGROUND: To characterize urinary isolates, the Clinical and Laboratory Standards Institute (CLSI) uses an amoxicillin breakpoint for cats based on plasma (not urine) drug concentrations (≤0.25 μg/mL), but a urine‐specific breakpoint for dogs exists (≤8 μg/mL). OBJECTIVES: To measure urine concentrations of amoxicillin and clavulanate after PO administration of amoxicillin‐clavulanate to cats, and to suggest updated urine‐specific susceptibility breakpoints for PO amoxicillin and amoxicillin‐clavulanate in cats. ANIMALS: Eleven healthy purpose‐bred cats. METHODS: Cats were given 3 62.5 mg doses of amoxicillin‐clavulanate PO q12h. After the third dose, urine was collected over 28 hours, recording urination time and volume. At least 3 urine samples were collected per cat. Liquid chromatography with mass spectrometry was used to determine the urine concentrations of amoxicillin and clavulanate. RESULTS: Amoxicillin concentrations were >8 μg/mL in all urine samples collected within 12 hours after administration (range, 31.6‐1351 μg/mL), with means of 929 μg/mL (0‐6 hours) and 532 μg/mL (6‐12 hours). The mean half‐life of amoxicillin in urine was 1.99 hours, and mean recovery was 30%. Clavulanate was detected in all urine samples, with mean half‐life of 2.17 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: Orally administered amoxicillin‐clavulanate resulted in urine amoxicillin concentrations above the cutoff (8 μg/mL) for wild‐type Escherichia coli in all cats. Because urine‐specific susceptibility testing breakpoints can be determined using urine concentrations, this information should allow new CLSI uropathogen susceptibility breakpoints for amoxicillin and amoxicillin‐clavulanate in healthy cats, increasing the urine breakpoint from ≤0.25 to ≤8 μg/mL.