In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 57, No. 2 ( 2013-02), p. 811-817
Abstract:
Escherichia coli is implicated in the pathogenesis of inflammatory bowel disease (IBD). Rifaximin, a nonabsorbable derivative of rifampin effective against E. coli , improves symptoms in mild-to-moderate IBD. However, rifaximin resistance can develop in a single step in vitro . We examined the prevalence and mechanisms of rifaximin resistance in 62 strains of E. coli isolated from the ileal mucosa of 50 patients (19 with ileal Crohn's disease [L1+L3], 6 with colonic Crohn's disease [L2] , 13 with ulcerative colitis [UC], 4 with symptomatic non-IBD diagnoses [NI] , and 8 healthy [H]). Resistance (MIC 〉 1,024 mg/liter) was present in 12/48 IBD-associated ileal E. coli strains. Resistance correlated with prior rifaximin treatment ( P 〈 0.00000001) but not with the presence of ileal inflammation ( P = 0.73) or E. coli phylogroup. Mutations in a 1,057-bp region of rpoB , which encodes the bacterial target of rifaximin, were identified in 10/12 resistant strains versus 0/50 sensitive strains ( P 〈 0.000000001) and consisted of seven amino acid substitutions. The efflux pump inhibitor Phe-Arg-β-naphthylamide (PAβN) lowered the MIC of 9/12 resistant strains 8- to 128-fold. Resistance was stable in the absence of rifaximin in 10/12 resistant strains after 30 passages. We conclude that IBD-associated ileal E. coli frequently manifest resistance to rifaximin that correlates with prior rifaximin use, amino acid substitutions in rpoB , and activity of PAβN-inhibitable efflux pumps, but not with the presence of ileal inflammation or E. coli phylogroup. These findings have significant implications for treatment trials targeting IBD-associated E. coli .
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.02163-12
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2013
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
