Digestive Diseases and Sciences

, Volume 58, Issue 6, pp 1676–1682 | Cite as

The Effect of Rifaximin on Gut Flora and Staphylococcus Resistance

  • Mi-Sung Kim
  • Walter Morales
  • Andres Ardila Hani
  • Sharon Kim
  • Gene Kim
  • Stacy Weitsman
  • Christopher Chang
  • Mark PimentelEmail author
Original Article



Rifaximin is a non-absorbed antibiotic relative of rifampicin. The location of effect and staphylococcal resistance are two recent potential concerns with rifaximin. In this study we evaluate the location of effect of rifaximin as well as the development of staphylococcal rifampicin resistance.


Rats were divided into three groups. Group 1 gavaged for 10 days with PBS, group 2 gavaged with rifaximin for 10 days, and group 3 gavaged with rifaximin for 10 days and housed for 30 days. In each group, stool was collected daily for quantitative culture of Staphylococcus spp. and coliforms. After euthanasia luminal bacterial counts were determined at multiple gut locations by qPCR. Rifampicin susceptibility was tested on Staphylococcus pre and post rifaximin.


At baseline, rats had a median of 2.90 × 106 cfu/ml Staphylococcus spp. in stool. After 10 days of rifaximin, this dropped to 1.20 × 105 cfu/ml (P < 0.01). With coliform counts, rats had a median of 1.86 × 104 cfu/ml at baseline which dropped to 2.2 × 103 cfu/ml (P < 0.01) after rifaximin. After cessation of rifaximin, coliform counts recovered within 3 days. When examining the total bacterial counts by qPCR, rifaximin reduced small bowel bacterial levels, but not colon. This reduction was sustained for 30 days. No colonies of Staphylococcus became resistant and only one colony was intermediate. The mean inhibitory concentration for rifampicin was not different before and after rifaximin.


Staphylococcal spp. fail to demonstrate resistance to rifampicin after rifaximin. The transient reductions in stool coliform counts recover while rifaximin appears to produce durable reductions in duodenal bacteria.


Rifaximin Staphylococcus Coliforms 



This investigator-initiated study was supported by a grant from Salix Pharmaceuticals. In addition, this work was further supported by a grant from the Beatrice and Samuel A. Seaver Foundation.

Conflict of interest

Cedars-Sinai has a licensing agreement with Salix Pharmaceuticals. In additions, Drs. Pimentel and Chang are consultants for Salix Pharmaceuticals.


  1. 1.
    Marchi E, Masigianni G, Montecci L, Burfani M, Cellai L. L/105, A new semisynthetic derivative of ryfamicin SV, synthesis and structure-activity relationship. Chemioterapia. 1983;2:38–50.Google Scholar
  2. 2.
    Descombe JJ, Dubourg D, Picard M, Palazzini E. Pharmacokinetic study of rifaximin after oral administration in healthy volunteers. Int J Clin Pharmacol Res. 1994;14:51–56.PubMedGoogle Scholar
  3. 3.
    Rizzello F, Rionchetti P, Venturi A, et al. Rifaximin systemic absorption in patients with ulcerative colitis. Eur J Clin Pharmacol. 1998;54:91–93.PubMedCrossRefGoogle Scholar
  4. 4.
    Jiang ZD, DuPont HL. In vitro and in vivo antibacterial activity—a review. Chemotherapy. 2005;51:67–72.PubMedCrossRefGoogle Scholar
  5. 5.
    Adachi JA, DuPont HL. Rifaximin: a novel non absorbed rifamycin for gastrointestinal disorders. Clin Infec Dis. 2006;42:541–547.CrossRefGoogle Scholar
  6. 6.
    Pimentel M, Lembo A, William DC, Salam Z, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Posserud I, Stotzer P-O, Bjornsson ES, Abrahamsson H, Simren M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut. 2007;56:802–808.PubMedCrossRefGoogle Scholar
  8. 8.
    Pyleris E, Giamarellos-Bourboulis EJ, Tzivras O, Koussoulas V, Barbatzas C, Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci. 2012;57:1321–1329.PubMedCrossRefGoogle Scholar
  9. 9.
    Valentin T, Leitner E, Rohn A, et al. Rifaximin intake leads to emergence of rifampin-resistant staphylococci. J Infect. 2011;62:34–38.PubMedCrossRefGoogle Scholar
  10. 10.
    Pimentel M, Morales W, Chua K, et al. Effects of rifaximin treatment and retreatment in non-constipated IBS subjects. Dig Dis Sci. 2011;56:2067–2072.PubMedCrossRefGoogle Scholar
  11. 11.
    DuPont HL, Jiang ZD. Influence of rifaximin treatment on susceptibility of intestinal gram-negative flora and enterococci. Clin Microbiol Infect. 2004;10:1009–1011.PubMedCrossRefGoogle Scholar
  12. 12.
    DeLeo C, Dftimiadi C, Schito GC. Rapid disappearance from the intestinal tract of bacteria resistant to rifaximin. Drugs Exp Clin Res. 1986;12:979–981.Google Scholar
  13. 13.
    Marchese A, Alerno A, Pesce A, Debbia EA, Schito GC. In vitro activity of rifaximin, metronidazole and vancomycin against Clostridium difficile and the rate of selection of spontaneously resistant mutants against representative anaerobic and aerobic bacteria, including ammonia-producing species. Chemotherapy. 2000;46:253–266.PubMedCrossRefGoogle Scholar
  14. 14.
    Hoover WW, Gerlach EH, Hoban DJ, Eliopoulos GM, Pfaller MA, Jones RN. Antimicrobial activity and spectrum of rifaximin, a new topical rifamycin derivative. Diagn Microbiol Infect Dis. 1993;16:111–118.PubMedCrossRefGoogle Scholar
  15. 15.
    Pimentel M, Chatterjee S, Chang C, et al. A new rat model links two contemporary theories in irritable bowel syndrome. Dig Dis Sci. 2008;53:982–989.PubMedCrossRefGoogle Scholar
  16. 16.
    Mohammadi T, Reesink HW, Vandenbroucke-Grauls CMJE, Savelkoul PHM. Optimization of real-time PCR assay for rapid and sensitive detection of eubacterial 16S ribosomal DNA in platelet concentrates. J Clin Microbiol. 2003;41:4796–4798.PubMedCrossRefGoogle Scholar
  17. 17.
    Johnson S, Schriever C, Galang M, Kelly CP, Gerding DN. Interruption of recurrent Clostridium difficile-associated diarrhea episodes by serial therapy with vancomycin and rifaximin. Clin Infect Dis. 2007;44:846–848.PubMedCrossRefGoogle Scholar
  18. 18.
    Frieri G, Pimpo MT, Scarpignato C. Management of colonic diverticular disease. Digestion. 2006;73:58–66.PubMedCrossRefGoogle Scholar
  19. 19.
    Fera G, Agostinacchio F, Nigro M, et al. Rifaximin in the treatment of hepatic encephalopathy. Eur J Clin Res. 1993;4:57–66.Google Scholar
  20. 20.
    Pimentel M. Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009;18:349–358.PubMedCrossRefGoogle Scholar
  21. 21.
    Guslandi M. Rifaximin in the treatment of inflammatory bowel disease. World J Gastroenterol. 2011;17:4643–4646.PubMedCrossRefGoogle Scholar
  22. 22.
    Shen B, Remzi FH, Lopez AR, Queener E. Rifaximin for maintenance therapy in antibiotic-dependent pouchitis. BMC Gastroenterol. 2008;8:26.PubMedCrossRefGoogle Scholar
  23. 23.
    Lanas A, Scarpignato C. Microbial flora in NSAID-induced intestinal damage: a role for antibiotics? Digestion. 2006;73:136–150.PubMedCrossRefGoogle Scholar
  24. 24.
    Hartmann G, Honikel K, Knusel F, Nuesch J. The specific inhibition of the DNA-directed RNA synthesis by ryfamycin. Biochim Biophys Acta. 1967;145:843–844.PubMedCrossRefGoogle Scholar
  25. 25.
    Livermore DM. Antibiotic resistance in staphylococci. Int J Antimicrob Agent. 2000;16:S3–S10.CrossRefGoogle Scholar
  26. 26.
    Tupin A, Gualtieri M, Roquet-Baneres F, Morichaud Z, Brodolin K, Leonetti JP. Resistance to rifampicin: at the crossroads between ecological, genomic and medical concerns. Int J Antimicrob Agents. 2010;35:519–523.PubMedCrossRefGoogle Scholar
  27. 27.
    Aubry-Damon H, Soussy C-J, Courvallin P. Characterization of mutations in the rpoB gene that confer rifampin resistance in Staphylococcus aureus. Antimicrob Agents Chemother. 1998;42:2590–2594.PubMedGoogle Scholar
  28. 28.
    Dreses-Werringloer U, Padubrin I, Kohler L, Hudson AP. Detection of nucleotide variability in rpoB in both rifampin-sensitive and rifampin-resistant strains of Chlamydia trachomatis. Antimicrob Agents Chemother. 2003;47:2316–2318.PubMedCrossRefGoogle Scholar
  29. 29.
    Yu J, Wu J, Francis KP, Purchio TF, Kadurugamuwa JL. Monitoring in vivo fitness of rifampicin-resistant Staphylococcus aureus mutants in a mouse biofilm infection model. J Antimicrob Chemother. 2005;55:528–534.PubMedCrossRefGoogle Scholar
  30. 30.
    Brigidi P, Swennen F, Rizzello F, et al. Effects of Rifaximin administration on the intestinal microbiota in patients with ulcerative colitis. J Chemother. 2002;14:290–295.PubMedGoogle Scholar
  31. 31.
    Stracciari JM, Venturini AP, Anfossi P, Marchi E, Stracciari GI. Sensitivity to rifaximin and rifampin of Mycobacterium tuberculosis isolated from guinea pigs treated orally with rifaximin. Chemioterapia. 1987;6:82–84.PubMedGoogle Scholar
  32. 32.
    William DL, Spring L, Collins L, et al. Contribution of rpo B mutations to development of rifamycin cross-resistance in Mycobacterium tuberculosis. Antimicrb Agents Chemother. 1998;42:1985–1987.Google Scholar
  33. 33.
    Soro O, Pesce A, Raggi M, Debbia EA, Schito GC. Selection of rifampin resistant mycobacterium tuberculosis does not occur in the presence if low concentrations of rifaximin. Clin Microbiol Infect. 1997;3:147–151.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Mi-Sung Kim
    • 1
  • Walter Morales
    • 2
  • Andres Ardila Hani
    • 2
  • Sharon Kim
    • 2
  • Gene Kim
    • 2
  • Stacy Weitsman
    • 2
  • Christopher Chang
    • 2
  • Mark Pimentel
    • 2
    Email author
  1. 1.Division of GastroenterologyCheongju St. Mary’s HospitalCheongjuKorea
  2. 2.GI Motility Program, Division of GastroenterologyCedars-Sinai Medical CenterLos AngelesUSA

Personalised recommendations