Evaluation of urine concentrations of amoxicillin and clavulanate in cats

J Vet Intern Med. 2021 Jan;35(1):456-461. doi: 10.1111/jvim.15991. Epub 2020 Dec 6.

Abstract

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.

Keywords: antimicrobial; pharmacokinetic; stewardship; urinary tract infection.

MeSH terms

  • Amoxicillin*
  • Amoxicillin-Potassium Clavulanate Combination*
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Clavulanic Acid
  • Dogs
  • Escherichia coli
  • Microbial Sensitivity Tests / veterinary

Substances

  • Anti-Bacterial Agents
  • Clavulanic Acid
  • Amoxicillin-Potassium Clavulanate Combination
  • Amoxicillin