Evaluation of the efficacy of a live Escherichia coli biotherapeutic product (asymptomatic bacteriuria E. coli 212)

Abstract

Background: Recurrent bacterial cystitis, often referred to as recurrent urinary tract infection (UTI), can be difficult to manage and alternative treatments are needed.

Hypothesis/objective: Intravesicular administration of asymptomatic bacteriuria (ASB) E. coli 212 will not be inferior to antimicrobial treatment for the management of recurrent UTI in dogs.

Animals: Thirty-four dogs with >1 UTI in the 12 months before presentation.

Methods: All dogs were deemed normal otherwise based on absence of abnormalities on physical examination, CBC, serum biochemical panel, and abdominal ultrasonography. Dogs were randomized to 1 of 2 treatment groups: Group 1 antimicrobials for 7 days or group 2 intravesicular administration of ASB E. coli 212. Owners were provided a voiding questionnaire regarding their dogs' clinical signs, which was completed daily for 14 days to assess clinical cure. Dogs were examined on days 7 and 14 to assess clinical cure, and urine specimens were submitted for urinalysis and bacterial culture.

Results: Clinical cure rates for ASB E. coli 212-treated dogs were not inferior to 7 days of antimicrobial treatment with a 12% margin of difference to determine non-inferiority. No significant difference was found between the treatment groups on days 7 and 14 in the proportion of dogs achieving ≥50% or ≥75% reduction in their clinical score compared with baseline.

Conclusions and clinical importance: These data suggest that intravesicular administration of ASB E. coli 212 is not inferior to antimicrobials for the treatment of recurrent UTI in dogs. This biotherapeutic agent could help alleviate the need for antimicrobials for some dogs with recurrent UTI, improving antimicrobial stewardship.

Keywords: antimicrobial resistance; cystitis; dog; urinary tract.

FIGURE 1

Bacterial isolates cultured from urine specimens from all dogs on day 0.

FIGURE 2

The clinical scores (median and range) of dogs in groups 1 and 2 on days 0 and 7.

FIGURE 3

Boundaries of noninferiority for the 2‐sided 95% confidence interval of the difference between group 1 (antimicrobial treatment) and group 2 (ASB E. coli 212) treatment and groups. The confidence interval for the difference between ASB E. coli 212 and antimicrobial treatment was located on the left of the noninferiority margin, therefore ASB E. coli 212 was noninferior to the antimicrobial treatment. Graph generated using the R package “confinterpret.” ASB, asymptomatic bacteriuria.