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.