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Background  Eradication of intramucosal  Escherichia coli  correlates with remission of periodic acid‐Schiff‐positive  E coli ‐associated granulomatous colitis (GC). Treatment failures attributed to multidrug resistant (MDR) bacteria necessitate alternative approaches.    Hypothesis/objectives  Determine clinical outcome of  E coli ‐associated GC in dogs treated based on antimicrobial susceptibility profiling and characterize  E coli  phylogeny and resistance mechanisms.    Animals  Twenty Boxers and 4 French Bulldogs with  E coli ‐associated GC.    Methods  Culture, antimicrobial susceptibility profiling, and molecular characterization of  E coli  were performed and response to treatment was evaluated.    Results  Initial biopsy sample culture yielded fluoroquinolone‐sensitive (FQ‐S)  E coli  from 9/24 dogs and fluoroquinolone‐resistant (FQ‐R)  E coli  from 15/24. All but 1 FQ‐R  E coli  were MDR with susceptibility to macrophage‐penetrating antimicrobials restricted to carbapenems in 13/15 dogs. Of 22/24 treated based on susceptibility profiling, 8/9 FQ‐S dogs had complete initial clinical response (CR) during fluoroquinolone (FQ) treatment, whereas 9/13 FQ‐R dogs had complete or partial response (PR) during meropenem or doxycycline treatment. In 5/9 FQ‐S and 12/13 FQ‐R dogs with follow‐up ≥3 months, CR was sustained in 5/5 FQ‐S (median, 25 months; range, 4‐46) whereas 6/12 FQ‐R had long‐term CR (median, 59 months; range 15‐102), 4/12 PR (median, 19 months; range, 5‐65), and 2/12 had no response (NR). Four dogs with long‐term follow‐up died within 4 years of diagnosis, including 2 euthanized for refractory colitis.  Escherichia coli  were genetically diverse. Fluoroquinolone resistance was associated with mutations in  gyrA  and  parC , with plasmid‐mediated resistance less common.    Conclusions and Clinical Importance  Antimicrobial treatment guided by susceptibility profiling was associated with positive long‐term outcomes in >80% of cases. Fluoroquinolone‐resistance was widespread and not clonal. Further study is required to optimize treatment for dogs with MDR  E coli ‐associated GC.

Escherichia coli ‐associated granulomatous colitis in dogs treated according to antimicrobial susceptibility profiling