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

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.