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Rifaximin: a unique gastrointestinal-selective antibiotic for enteric diseases
Open accessAbstract
PURPOSE OF REVIEW: Rifaximin is gaining attention for its potential activity in a multitude of gastrointestinal diseases. We review the unique pharmaceutical properties of this antibiotic and the published evidence in the literature regarding the use of rifaximin for different gastrointestinal disorders. RECENT FINDINGS: Rifaximin is a gastrointestinal-selective antibiotic with a broad spectrum of antimicrobial activity, an excellent safety profile, minimal drug interactions, and negligible impact on the intestinal microbiome. Rifaximin is currently approved in the United States for the treatment of travelers' diarrhea caused by noninvasive diarrheagenic Escherichia coli and is approved in more than 30 other countries for a variety of gastrointestinal disorders. Considerable research with this medication has been conducted for the treatment and prevention of travelers' diarrhea, the treatment of portal systemic encephalopathy, Clostridium difficile infection, small bowel intestinal overgrowth, irritable bowel syndrome, inflammatory bowel disease, pouchitis, and colonic diverticular disease. SUMMARY: Rifaximin is effective for the treatment of travelers' diarrhea and can be considered as the treatment of choice for uncomplicated travelers' diarrhea. When invasive travelers' diarrhea pathogens are suspected, an alternative antibiotic should be administered. Rifaximin appears promising as a chemoprophylaxis for travelers' diarrhea and as a treatment of portal systemic encephalopathy. This antibiotic may be effective for other gastrointestinal diseases, but more well designed clinical studies are needed to confirm its efficacy for these off-label indications. Future studies will determine whether the development of significant bacterial resistance will limit rifaximin use.
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“Rifaximin is a nonabsorbable antibiotic with broad-spectrum antimicrobial activity and an excellent safety profile113 that was initially approved for the treatment of traveller’s diarrhoea but is increasingly used for the prevention of hepatic encephalopathy99.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [113]
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“Acute diarrhea unrelated to travel Although rifaximin was approved only for the treatment of travelers’ diarrhea in the United States, it is indicated for infectious diarrhea independent of the travel history in most other countries where rifaximin is marketed, including South Korea [Koo and Dupont, 2010].”
BackgroundInfluentialCyclic antibiotic therapy for diverticular disease: a critical reappraisal.
Zullo, A., Hassan, C., Maconi, G., Manes, G., Tammaro, G., Francesco, V. D., Annibale, B., Ficano, L., Buri, L., Gatto, G., et al. (2010) · PubMed · Cited by 27
Probing gut‐brain links in Alzheimer's disease with rifaximin
Suhocki, P. V., Ronald, J., Diehl, A. M., Murdoch, D. M., & Doraiswamy, P. M. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12225 · Cited by 27
TMIO-PyrImid Hybrids are Profluorescent, Site-Directed Spin Labels for Nucleic Acids
Chalmers, B. A., Saha, S., Nguyen, T., McMurtrie, J. C., Sigurdsson, S. T., Bottle, S. E., & Masters, K. (2014) · Organic Letters · doi:10.1021/ol502003a · Cited by 27
Elsheikh, M., Sabagh, A. E., Mohamed, I. B., Bhongade, M., Hassan, M. M., & Jalal, P. K. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i46.6028 · Cited by 28
“Its primary function is to specifically target and eradicate harmful bacteria in the intestinal tract[184].”
Solvent and catalyst‐free synthesis of imidazo[1,2‐a]pyridines by grindstone chemistry
Godugu, K., & Reddy, N. C. G. (2020) · Journal of Heterocyclic Chemistry · doi:10.1002/jhet.4164 · Cited by 26
Gut Microbiota, Peroxisome Proliferator-Activated Receptors, and Hepatocellular Carcinoma
Yu, Q., Wu, L., Ji, J., Feng, J., Dai, W., Li, J., Wu, J., & Guo, C. (2020) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s277870 · Cited by 27
Han, S. S., Shannahan, S. E., & Pellish, R. S. (2015) · Journal of Intensive Care Medicine · doi:10.1177/0885066615594344 · Cited by 26
“This antibiotic is not absorbed by the GI tract nor inactivated by gastric secretions while exerting its effects only within the intestinal lumen.(83,84) There have been small clinical trials testing its effects against C difficile, which have shown it to be fairly effective.”
BackgroundNovel prevention strategies for bacterial infections in cirrhosis
Yan, K. G., & García–Tsao, G. (2016) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2016.1145663 · Cited by 26
“[31,32] However, a recent study shows that, rather than changing the stool microbiome, it seems to have a direct effect on bacterial function by impairing their ability to translocate.”
BackgroundPayra, S., Saha, A., Wu, C., Selvaratnam, B., Dramstad, T., Mahoney, L., Verma, S. K., Thareja, S., Koodali, R. T., & Banerjee, S. (2016) · New Journal of Chemistry · doi:10.1039/c6nj02134d · Cited by 26
Emerging role of probiotics and antimicrobials in the management of irritable bowel syndrome
Cash, B. D. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2014.908278 · Cited by 26
Chen, Z., Liang, P., Xu, F., Qiu, R., Tan, Q., Long, L., & Ye, M. (2019) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.9b01188 · Cited by 25
Bile acid–gut microbiota crosstalk in irritable bowel syndrome
Gu, Y., Li, L., Yang, M., Liu, T., Song, X., Qin, X., Xu, X. J., Liu, J., Wang, B., & Cao, H. (2022) · Critical Reviews in Microbiology · doi:10.1080/1040841x.2022.2058353 · Cited by 26
Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications
Chang, L., Liu, Y., Li, H., Yan, J., Wu, W., Chen, N., Ma, C., Zhao, X., Chen, J., & Zhang, J. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1717696 · Cited by 26
“It broadly suppresses enteric pathogens while sparing many commensal organisms (Koo and DuPont, 2010).”
Rifaximin for the prevention of spontaneous bacterial peritonitis
Kalambokis, G. N. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i14.1700 · Cited by 24
Chronic Intestinal Pseudo-Obstruction: Is There a Connection with Gut Microbiota?
Radocchia, G., Neroni, B., Marazzato, M., Capuzzo, E., Zuccari, S., Pantanella, F., Zenzeri, L., Evangelisti, M., Vassallo, F., Parisi, P., et al. (2021) · Microorganisms · doi:10.3390/microorganisms9122549 · Cited by 22
“Nevertheless, the most recent recommended agent is rifaximin, a poorly absorbed antibiotic that, differently to the others, exerts nontraditional effects on the gut microbiota in addition to bactericidal/bacteriostatic activity, producing lower bacterial resistance than traditional agents [41,42].”
BackgroundA Chemoselective N-Arylation Reaction of 2-Aminopyridine Derivatives with Arynes
Cheng, B., Wei, J., Zu, B., Zhao, J., Wang, T., Duan, X., Wang, R., Li, Y., & Zhai, H. (2017) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.7b01405 · Cited by 20
Diagnosis of symptomatic uncomplicated diverticular disease and the role of Rifaximin in management.
Maconi, G. (2017) · Acta bio-medica dell'Ateneo parmense/Acta biomedica · doi:10.23750/abm.v88i1.6360 · Cited by 20
“One reason for the low frequency of adverse events is that the alpha polymorphic form of rifaximin has negligible gut absorption and systemic availability (52).”
BackgroundBoulos, M., Mousa, R. S., Jeries, N., Simaan, E., Alam, K., Bulus, B., & Assy, N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26073448 · Cited by 22
“We advise the investigation of this drug since it is gut selective with almost no systemic bioavailability (less than 0.04% in blood stream) and could avoid possible antibiotics resistance in the long-term effects [278,282,283].”
InfluentialWeight Loss in Parkinson’s Disease: No Evidence for Role of Small Intestinal Bacterial Overgrowth
DiBaise, J. K., Crowell, M. D., Driver‐Dunckley, E. D., Mehta, S. H., Hoffman‐Snyder, C., Lin, T. P., & Adler, C. H. (2018) · Journal of Parkinson s Disease · doi:10.3233/jpd-181386 · Cited by 19
“Rifaximin (Xifaxin ® , Salix Pharmaceuticals Inc.), is an orally administered, semi-synthetic, non-systemic antibiotic [17] and is commonly used in the treatment of SIBO, although it is not United States Food and Drug Administration-approved for this indication.”
Reddy, K. R., Gupta, A. P., & Das, P. (2016) · Asian Journal of Organic Chemistry · doi:10.1002/ajoc.201600120 · Cited by 18
Gupta, A., Sasan, S., Kour, A., Nelofar, N., Mondhe, D. M., & Kapoor, K. K. (2019) · Synthetic Communications · doi:10.1080/00397911.2019.1605445 · Cited by 18
Rifaximin in the Treatment of Irritable Bowel Syndrome
Farrell, D. J. (2013) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0b013e31827559a3 · Cited by 17
Garrido‐Mesa, J., Algieri, F., Rodríguez‐Nogales, A., Vezza, T., Utrilla, M. P., García, F., Chueca, N., Rodríguez‐Cabezas, M. E., Garrido‐Mesa, N., & Gálvez, J. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.07.044 · Cited by 17
Discovery and Development of Antibacterial Agents: Fortuitous and Designed
Kapoor, B., Gulati, M., Kaur, R., Rani, P., Atanasov, A. G., Alzahrani, Q. E., Gupta, R., & Chawla, P. (2021) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1570193x19666211221150119 · Cited by 16
Buldain, D., Castillo, L. G., Buchamer, A., Aliverti, F., Bandoni, A. L., Marchetti, L., & Mestorino, N. (2020) · Frontiers in Veterinary Science · doi:10.3389/fvets.2020.00344 · Cited by 15
“RIF has been traditionally applied in human medicine to treat travelers’ diarrhea (15, 16) and hepatic encephalopathy (17).”
BackgroundKhezerloo, E., Hekmat, F., Shahrokhian, S., & zad, A. I. (2023) · Diamond and Related Materials · doi:10.1016/j.diamond.2023.110280 · Cited by 14
Metadata
- Authors
- Koo, H. L., & DuPont, H. L.
- Affiliations
- Baylor College of Medicine (US)
- Baylor St. Luke's Medical Center (US)
- Corresponding author
- Koo, Hoonmo L
- ORCID
- DuPont, Herbert L
- Venue
- Current Opinion in Gastroenterology
- Published
- 2010-01
- Volume
- 26
- Issue
- 1
- Pages
- 17-25
- ISSN
- 0267-1379 (ISSN-L)
- PMC
- PMC4737517
- OpenAlex
- W2121076704
- Cited by
- 189
- References
- 76
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 13 · 2023: 8 · 2022: 15 · 2021: 13 · 2020: 11 · 2019: 9 · 2018: 10 · 2017: 7 · 2016: 10 · 2015: 12 · 2014: 11 · 2013: 10 · 2012: 18
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Houston
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK084513)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Keywords
- rifaximin, traveler's diarrhea, portal-systemic encephalopathy, Clostridium difficile infection, small intestinal bacterial overgrowth, irritable bowel syndrome, inflammatory bowel disease, pouchitis, colonic diverticular disease, chemoprophylaxis, gut microbiota, drug resistance
- MeSH terms
- Rifaximin, Anti-Infective Agents, Bacterial Infections, Dose-Response Relationship, Drug, Drug Administration Schedule, Dysentery, Female, Follow-Up Studies, Gastroenteritis, Humans, Male, Rifamycins, Travel, Randomized Controlled Trials as Topic, Treatment Outcome, Risk Assessment
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