Rifaximin--a novel antimicrobial for enteric infections.

Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Journal of Infection (Impact Factor: 4.02). 03/2005; 50(2):97-106. DOI: 10.1016/j.jinf.2004.05.019
Source: PubMed

ABSTRACT Rifaximin is a poorly absorbed rifamycin antimicrobial drug with in vitro activity against Gram-positive, Gram-negative and anaerobic bacteria. The minimal concentration that inhibits 90% of strains of bacterial pathogens (MIC90) ranges between 32 and 64 microg/ml. Less than 1% of the drug is absorbed after oral administration. After three days of therapy, the average fecal level of this drug is 8000 microg/g of stool. Selection of resistant mutants, a problem with the related rifampin, appears to be unusual with rifaximin. Rifaximin shortens the duration of travelers' diarrhea and non-dysenteric diarrheal illness due to enterotoxigenic, enteroaggregative E. coli and Shigella sonnei without major alteration of aerobic fecal flora and without important side effects. The drug has been successfully used in preliminary studies of small bowel bacterial overgrowth syndrome and hepatic encephalopathy. To explain the beneficial effect of the drug on bacterial diarrhea without change in colonic flora or high rates of pathogen eradication, rifaximin may be more active against pathogens in the small bowel rather than the colon and/or the drug may alter the virulence of enteric pathogens in addition to organism inhibition.

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    ABSTRACT: Many environmental bacteria are multidrug-resistant and represent a reservoir of ancient antibiotic resistance determinants, which have been linked to genes found in pathogens. Exploring the environmental antibiotic resistome, therefore, reveals the diversity and evolution of antibiotic resistance and also provides insight into the vulnerability of clinically used antibiotics. In this study, we describe the identification of a highly conserved regulatory motif, the rifampin (RIF) -associated element (RAE), which is found upstream of genes encoding RIF-inactivating enzymes from a diverse collection of actinomycetes. Using gene expression assays, we confirmed that the RAE is involved in RIF-responsive regulation. By using the RAE as a probe for new RIF-associated genes in several actinomycete genomes, we identified a heretofore unknown RIF resistance gene, RIF phosphotransferase (rph). The RPH enzyme is a RIF-inactivating phosphotransferase and represents a new protein family in antibiotic resistance. RPH orthologs are widespread and found in RIF-sensitive bacteria, including Bacillus cereus and the pathogen Listeria monocytogenes. Heterologous expression and in vitro enzyme assays with purified RPHs from diverse bacterial genera show that these enzymes are capable of conferring high-level resistance to a variety of clinically used rifamycin antibiotics. This work identifies a new antibiotic resistance protein family and reinforces the fact that the study of resistance in environmental organisms can serve to identify resistance elements with relevance to pathogens.
    Proceedings of the National Academy of Sciences 04/2014; DOI:10.1073/pnas.1402358111 · 9.81 Impact Factor
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    ABSTRACT: R ifaximin is a non-systemic, broad-spectrum antibiotic that acts against gram-positive, gram-negative, and anaerobic bacteria. Clinical stud-ies indicate that rifaximin is beneficial in treating irritable bowel syndrome (IBS). The mechanism responsible for the beneficial effects of rifaximin is not clear. In a recent study, we reported that rifaximin alters the bacterial population in the ileum of rats, leading to a rela-tive abundance of Lactobacillus species. These changes prevent gut inflamma-tion and visceral hyperalgesia caused by chronic stress. To more closely mirror human clinical studies in which rifaxi-min is used to treat IBS symptoms, we performed additional studies and showed that rifaximin reversed mucosal inflam-mation and barrier dysfunction evoked by chronic stress. These beneficial effects were accompanied by a striking increase in the abundance of Lactobacillaceae and a marked reduction in the number of seg-mented filamentous bacteria after rifaxi-min treatment. These microbial changes may contribute to the antiinflammatory effects of rifaximin on the intestinal mucosa. Irritable bowel syndrome (IBS) is a common gastrointestinal disorder affect-ing 10–15% of the population in the Western world. The pathophysiology of IBS is not well understood. 1-3 Many IBS patients have motility abnormalities and/ or visceral hypersensitivity. Recent studies indicate that IBS may be associated with subclinical mucosal inflammation in the ileum and colon, which is characterized by cellular infiltration of CD3 and CD25 lymphocytes and mast cells. 4-8 These inflammatory changes are accompanied by increased cytokines in the mucosa or peripheral circulation. 9,10 There is accu-mulating evidence that patients with IBS also have increased intestinal permeabil-ity. 11,12 These patients with impaired bar-rier function have an increased functional bowel disorder severity index (FBDSI) score and are hypersensitive to painful stimuli. 12 It is conceivable that sustained enhancement of paracellular permeability may facilitate the passage of luminal bac-teria or their metabolic products through the barrier, leading to mucosal inflamma-tion and visceral hypersensitivity. Alteration of the gut microbiota may play an important role in the pathogen-esis of IBS symptoms. Up to 20–25% of patients develop IBS symptoms fol-lowing an episode of enteric infection. 7,13
    Gut Microbes 08/2014; 5(4):1-5. DOI:10.4161/gmic.32130