Effect of amoxicillin-clavulanic acid on clinical scores, intestinal microbiome, and amoxicillin-resistant Escherichia coli in dogs with uncomplicated acute diarrhea

J Vet Intern Med. 2020 May;34(3):1166-1176. doi: 10.1111/jvim.15775. Epub 2020 Apr 23.

Abstract

Background: Despite limited evidence of efficacy, antibiotic treatment is still frequently prescribed in dogs with uncomplicated acute diarrhea (AD).

Objective: To assess whether amoxicillin-clavulanic acid has a clinical benefit, an effect on the fecal microbiome, and the proportion of amoxicillin-resistant Escherichia coli in dogs with AD.

Animals: Sixteen dogs with AD of <3 days duration.

Methods: Prospective, placebo-controlled, double-blinded study. Clinical scores were compared between client-owned dogs randomly assigned to an antibiotic (AG) or a placebo (PG) group. The intestinal microbiome was analyzed using quantitative PCR assays. Amoxicillin-resistant fecal E. coli were assessed semiquantitatively with microbiological methods.

Results: There was no difference in clinical recovery between treated dogs or controls (CADS index day 10: AG group median: 2 (range: 1-3; CI [1.4; 2.6]); PG group median: 1.6 (range: 1-3; CI [1.1; 2.4]); P > .99). All dogs gained normal clinical scores (CADS index ≤3) after 1 to 6 days (median 2 days) after presentation. There was no significant difference in the fecal dysbiosis index (during treatment: AG mean -2.6 (SD 3.0; CI [-5.1; 0.0]); PG mean -0.8 (SD 4.0; CI [-4.2; 2.5]; P > .99) or its bacterial taxa. The proportion of resistant fecal E. coli increased (to median: 100%; range: 35%-100%) during treatment with amoxicillin-clavulanic acid and was still increased (median: 10%; range 2%-67%) 3 weeks after treatment, both of which were significantly higher proportions than in the placebo group for both time points (during treatment AG median 100% versus PG median 0.2% (P < .001); after treatment AG median 10% versus PG median 0.0% (P = .002)).

Conclusions and clinical importance: Our study suggests that treatment with amoxicillin-clavulanic acid confers no clinical benefit to dogs with AD, but predisposes the development of amoxicillin-resistant E. coli, which persist for as long as 3 weeks after treatment. These findings support international guideline recommendations that dogs with diarrhea should not be treated with antimicrobials unless there are signs of sepsis.

Keywords: antibiotic; antimicrobial; canine; diarrhea; resistance; sensitivity.

Publication types

  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Amoxicillin / pharmacology
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Animals
  • Anti-Bacterial Agents / therapeutic use
  • Diarrhea / drug therapy
  • Diarrhea / veterinary*
  • Dog Diseases / drug therapy*
  • Dog Diseases / microbiology
  • Dogs
  • Drug Resistance, Bacterial / drug effects
  • Escherichia coli / drug effects*
  • Gastrointestinal Microbiome / drug effects*
  • Microbial Sensitivity Tests / veterinary
  • Prospective Studies

Substances

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