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Multidrug Resistance Is Common in Escherichia coli Associated with Ileal Crohn's Disease

Dogan, Belgin PhD*; Scherl, Ellen MD; Bosworth, Brian MD; Yantiss, Rhonda MD; Altier, Craig DVM, PhD; McDonough, Patrick L. PhD; Jiang, Zhi-Dong MD, PhD§; DuPont, Herbert L. MD§; Garneau, Philippe MS; Harel, Josee PhD; Rishniw, Mark BVSc, PhD*; Simpson, Kenneth W. BVM&S, PhD*

doi: 10.1002/ibd.22971
Original Basic Science Articles

Background: Escherichia coli is increasingly implicated in the pathogenesis of ileal Crohn's disease (ICD), offering a potential therapeutic target for disease management. Empirical antimicrobial targeting of ileal E. coli has advantages of economy and speed of implementation, but relies on uniform susceptibility of E. coli to routinely selected antimicrobials to avoid apparent treatment failure. Therefore, we examined the susceptibility of ileal E. coli to such antimicrobials.

Methods: E. coli from 32 patients with ICD and 28 with normal ileum (NI) were characterized by phylogroup, pathotype, antimicrobial susceptibility, and presence of antimicrobial resistance genes.

Results: In all, 17/32 ICD and 12/28 NI patients harbored ≥1 E. coli strain; 10/24 E. coli strains from ICD and 2/14 from NI were nonsuscepti-ble to ≥1 antimicrobial in ≥3 categories (multidrug-resistant). Resistance to amoxicillin/clavulanic-acid, cefoxitin, chloramphenicol, ciprofloxa-cin, gentamicin, and rifaximin was restricted to ICD, with 10/24 strains from 8/17 patients resistant to ciprofloxacin or rifaximin (P < 0.01). Adherent-invasive E. coli (AIEC) were isolated from 8/32 ICD and 5/28 NI, and accounted for 54% and 43% of E. coli strains in these groups. In all, 8/13 AIEC strains from ICD (6/8 patients) versus 2/6 NI (2/5 patients) showed resistance to the macrophage-penetrating antimicrobials ciprofloxacin, clarithromycin, rifampicin, tetracycline, and trimethoprim/sulfamethoxazole. Resistance was associated with tetA, tetB, tetC, bla- TEM , bla oxa-1 , sulI, sulII, dhfrI, dhfrVII, ant(3″)-Ia, and catI genes and prior use of rifaximin (P < 0.01).

Conclusions: ICD-associated E. coli frequently manifest resistance to commonly used antimicrobials. Clinical trials of antimicrobials against E. coli in ICD that are informed by susceptibility testing, rather than empirical selection, are more likely to demonstrate valid outcomes of such therapy.

Article first Published online 16 April 2012

*Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York

Jill Roberts Center for Inflammatory Bowel Disease, Weill Medical College of Cornell University, New York, New York

Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York

§University of Texas Health Science Center at Houston, School of Public Health, Houston, Texas

Department of Pathology and Microbiology, Faculty of Veterinary Medicine, University of Montreal, Montreal, Canada.

Reprints: Kenneth W. Simpson or Belgin Dogan, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY (e-mail: or

Supported by a grant from NY Presbyterian/Weill Cornell Medical College and the Jill Roberts Center for Inflammatory Bowel Disease.

Received February 05, 2012

Accepted March 12, 2012

© Crohn's & Colitis Foundation of America, Inc.
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