Rifaximin Resistance in Escherichia coli Associated with Inflammatory Bowel Disease Correlates with Prior Rifaximin Use, Mutations in rpoB,

[kiny]

http://aac.asm.org/content/57/2/811.long

Rifaximin Resistance in Escherichia coli Associated with Inflammatory Bowel Disease Correlates with Prior Rifaximin Use, Mutations in rpoB, and Activity of Phe-Arg-β-Naphthylamide-Inhibitable Efflux Pumps.

February 2013

Kothary V, Scherl EJ, Bosworth B, Jiang ZD, Dupont HL, Harel J, Simpson KW, Dogan B.

College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA.

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.

 

[JDTM]

Hey there kiny -- as someone who has taken a short course of Rifaximin before, should these findings dissuade me from trying it again if I feel like a flare is coming back on? It's been quite a while since I last took it, and from what I recall it helped at least a little. Not sure if it'll be a dismal failure next time, or if there's only a small chance of that happening as it was so long ago. Hopefully you can give me some of your scientific-article expertise in layman's terms. Thanks!!

(Of course, here's hoping I won't have to take any antibiotics again at all for IBD, but then again, who knows.)

 

[kiny]

No that's not enough to say no if it helps you. Ideally you would check people who have AIEC, you would isolate the bacteria (through biopsy or other means), you would check the strain against an antibiotic and test susceptibility, but I know 99% of GI do not do this, do not know how to do this and just give antibiotics in the hopes it works, and if it works, yes take it imo.

Although be aware that going off and on the antibiotic is, like any antibiotics, going to result in resistance, Rifaximin is quite a safe antibiotic with low bioavailability, so maybe discuss how long you plan to use it with your doctor etc beforehand.

This study above is more of a warning to other studies that are going to test Rifaximin, most studies do not use ideal setting. In their previous studies by the same authors they have detailed that ideally you would only use people with specific ileum disease, you would isolate the strains and test them again rifaximin and you would test resistance, but sadly we are not there yet, crohn's disease needs to be treated more on an individual basis than it is now. But don't let this stop you from using what helps you.

 

[JDTM]

Good call. I know that it's a bad idea in general to take antibiotics often, as it can often result in resistance. However, my course of Rifaximin was fairly short (2 weeks), and I would be hesitant to try a second course in rapid succession. Again, thanks for the link and the info!!