title: Multidrug resistance is common in Escherichia coli associated with ileal Crohn's disease.
abstract: 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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Belgin
authors.initials: B
authors.lastname: Dogan
authors.forename: Ellen
authors.initials: E
authors.lastname: Scherl
authors.forename: Brian
authors.initials: B
authors.lastname: Bosworth
authors.forename: Rhonda
authors.initials: R
authors.lastname: Yantiss
authors.forename: Craig
authors.initials: C
authors.lastname: Altier
authors.forename: Patrick L
authors.initials: PL
authors.lastname: McDonough
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Jiang
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Dupont
authors.forename: Philippe
authors.initials: P
authors.lastname: Garneau
authors.forename: Josee
authors.initials: J
authors.lastname: Harel
authors.forename: Mark
authors.initials: M
authors.lastname: Rishniw
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Simpson
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003424:Crohn Disease / Q000188:drug therapy / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000382:microbiology*; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins