The Experts below are selected from a list of 4671 Experts worldwide ranked by ideXlab platform
Herbert L. Dupont - One of the best experts on this subject based on the ideXlab platform.
-
Review article: the antimicrobial effects of Rifaximin on the gut microbiota.
Alimentary Pharmacology & Therapeutics, 2015Co-Authors: Herbert L. DupontAbstract:SummaryBackground Disruption of the gut microbiota through use of systemic antimicrobials or activation of the mucosal inflammatory response by pathogens can cause dysregulation of the intestinal mucosa. Aim To explore the mechanisms of action of Rifaximin that may underlie its clinical benefits in travellers’ diarrhoea (TD). Methods A literature search was performed using the terms ‘Rifaximin’ and ‘L/105’ in combination with the terms ‘in vitro activity’, ‘diarrhea’, ‘microbiota’ and ‘gut flora’. Results Rifaximin has been traditionally identified as a nonsystemic, broad-spectrum, bactericidal antibiotic. Evidence shows that the activity of Rifaximin against enteropathogens in this setting is likely enhanced by its increased solubility in the presence of bile acids in the small intestine. Results of clinical studies show that although Rifaximin is efficacious in TD, a clinical cure often occurs without apparent bacterial eradication and with minimal effect on the gut microbiota, suggesting an effect of Rifaximin other than direct antibiotic activity. Conclusions Although definitive studies on the effect of Rifaximin on the gut microbiota in large cohorts of healthy volunteers or patients have not been published, pre-clinical studies provide some insight. These studies have shown that Rifaximin may have effects on both the pathogen and host, including direct effects on pathogenic bacteria (such as reducing the expression of bacterial virulence factors) and indirect effects on the host (such as inhibiting bacterial attachment and internalisation at the intestinal mucosa and reducing mucosal inflammation).
-
Introduction: understanding mechanisms of the actions of Rifaximin in selected gastrointestinal diseases.
Alimentary Pharmacology & Therapeutics, 2015Co-Authors: Herbert L. DupontAbstract:SummaryBackground Historically, the beneficial effects of the nonsystemic oral agent Rifaximin on various gastrointestinal (GI) disorders have been attributed to direct antibiotic activity on gut microbiota. However, data are accumulating to suggest that other nonantibacterial effects may be involved in Rifaximin efficacy. Aim To explore the mechanisms of action of Rifaximin that may underlie its clinical benefits in travellers’ diarrhoea, hepatic encephalopathy and other cirrhosis complications, inflammatory bowel diseases, and irritable bowel syndrome with diarrhoea. Methods Gastroenterology experts convened a round-table discussion to address clinical and pre-clinical Rifaximin data pertaining to select GI diseases and the potential mechanisms of action that underlie Rifaximin efficacy profiles. As preparation, the literature was searched for publications related to Rifaximin, its mechanisms of action, and its efficacy in travellers’ diarrhoea, hepatic encephalopathy and other cirrhosis-related complications, inflammatory bowel diseases and irritable bowel syndrome. Results Gut microbiota dysbiosis and proinflammatory activities are thought to significantly contribute to disease pathophysiology of these conditions. Rifaximin may resolve gut microbiota dysbiosis by promoting GI colonisation of beneficial bacterial species without drastic alterations in overall diversity. Rifaximin-induced changes in the production and metabolism of bacteria-produced agents (e.g. deoxycholic acid, lipopolysaccharides) also may help preserve normal gut microbiota. Rifaximin may suppress local and systemic inflammatory processes by preserving epithelial function (e.g. limiting bacterial translocation), modulating bacterial virulence and reducing proinflammatory cytokine production. Conclusion The commonality of pathological mechanisms underlying multiple GI diseases and the ability of Rifaximin to modulate the gut microenvironment (i.e. gut microenvironment modulator) may explain its diverse efficacy profile.
-
Therapeutic Effects and Mechanisms of Action of Rifaximin in Gastrointestinal Diseases
Mayo Clinic proceedings, 2015Co-Authors: Herbert L. DupontAbstract:Emerging preclinical and clinic evidence described herein suggests that the mechanism of action of Rifaximin is not restricted to direct antibacterial effects within the gastrointestinal tract. Data from this study were derived from general and clinical trial-specific PubMed searches of English-language articles on Rifaximin available through December 3, 2014. Search terms included Rifaximin alone and in combination (using the Boolean operation "AND") with travelers' diarrhea, hepatic encephalopathy, liver cirrhosis, irritable bowel syndrome, inflammatory bowel disease, and Crohn's disease. Rifaximin appears to reduce bacterial virulence and pathogenicity by inhibiting bacterial translocation across the gastrointestinal epithelial lining. Rifaximin was shown to decrease bacterial adherence to epithelial cells and subsequent internalization in a bacteria- and cell type-specific manner, without an alteration in bacterial counts, but with a down-regulation in epithelial proinflammatory cytokine expression. Rifaximin also appears to modulate gut-immune signaling. In animal models of inflammatory bowel disease, Rifaximin produced therapeutic effects by activating the pregnane X receptor and thereby reducing levels of the proinflammatory transcription factor nuclear factor κB. Therefore, for a given disease state, Rifaximin may act through several mechanisms of action to exert its therapeutic effects. Clinically, Rifaximin 600 mg/d significantly reduced symptoms of travelers' diarrhea (eg, time to last unformed stool vs placebo [32.0 hours vs 65.5 hours, respectively; P=.001]). For the prevention of hepatic encephalopathy recurrence, data indicate that treating 4 patients with Rifaximin 1100 mg/d for 6 months would prevent 1 episode of hepatic encephalopathy. For diarrhea-predominant irritable bowel syndrome, a significantly greater percentage (40.7%) of patients treated with Rifaximin 1650 mg/d for 2 weeks experienced adequate global irritable bowel syndrome symptom relief vs placebo (31.7%; P
-
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
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Vishesh Kothary, Herbert L. Dupont, Zhi Dong Jiang, Ellen Scherl, Brian P Bosworth, Josee Harel, Kenneth W Simpson, Belgin DoganAbstract: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.
-
a randomized double blind placebo controlled pilot study to assess the ability of Rifaximin to prevent recurrent diarrhoea in patients with clostridium difficile infection
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Zhi Dong Jiang, Kevin W. Garey, Shashank S Ghantoji, Dhara N Shah, Musarat Habib, Vaneet Arora, Herbert L. DupontAbstract:BACKGROUND Uncontrolled case series have demonstrated decreased Clostridium difficile infection (CDI) recurrence in patients given Rifaximin after standard antibiotic therapy. However, clinical trials assessing whether Rifaximin decreases recurrent diarrhoea in patients with CDI have not been performed. The purpose of this study was to assess rates of recurrent diarrhoea in patients with CDI given Rifaximin versus placebo immediately after standard therapy. METHODS This was a randomized, double-blind, placebo-controlled pilot study. Patients with CDI and a Horn's index ≥1 were randomized to receive Rifaximin 400 mg three times daily or placebo for 20 days given immediately after finishing standard anti-CDI antibiotics. Patients were followed for 3 months and assessed for recurrent diarrhoea that included CDI recurrence (return of diarrhoea with a positive toxin test) and patient self-reported return of non-CDI diarrhoea after a period of wellness. RESULTS Sixty-eight patients aged 61 ± 18 years (50% male) were given Rifaximin (n = 33) or placebo (n = 35). Twenty-four of 68 (35%) patients had recurrent diarrhoea either due to recurrent CDI (23.5%) or self-reported diarrhoea (11.5%). Recurrent diarrhoea occurred in 17 of 35 (49%) patients given placebo and 7 of 33 (21%) given Rifaximin (P = 0.018). CDI recurrence occurred in 11 of 35 (31%) patients given placebo and 5 of 33 (15%) patients given Rifaximin (P = 0.11). Self-reported diarrhoea occurred in 6 of 35 (17%) of patients given placebo and 2 of 33 (6%) given Rifaximin (P = 0.15). CONCLUSIONS Patients with CDI given a Rifaximin chaser regimen experienced a decreased incidence of recurrent diarrhoea compared with placebo.
David N. Taylor - One of the best experts on this subject based on the ideXlab platform.
-
systemic pharmacokinetics of Rifaximin in volunteers with shigellosis
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: David N. Taylor, Anna P Durbin, Robert Haake, Robin Mckenzie, Colleen Carpenter, Louis A BourgeoisAbstract:Rifaximin is an oral antibiotic indicated for treatment of traveler's diarrhea. Rifaximin pharmacokinetics were evaluated in individuals challenged with Shigella flexneri. Peak plasma Rifaximin concentrations were low after nine consecutive doses, and no accumulation was observed. Rifaximin serum levels were minimal and similar to those previously reported in studies of healthy volunteers.
-
a randomized double blind multicenter study of Rifaximin compared with placebo and with ciprofloxacin in the treatment of travelers diarrhea
American Journal of Tropical Medicine and Hygiene, 2006Co-Authors: David N. Taylor, Robert Haake, Louis A Bourgeois, Zhi Dong Jiang, Charles D. Ericsson, Robert Steffen, Jane Halpern, Herbert L. DupontAbstract:Rifaximin was compared with placebo and ciprofloxacin for treatment of travelers' diarrhea in a randomized, double-blind clinical trial. Adult travelers (N = 399) consulting travel clinics in Mexico, Guatemala, and India were randomized to receive Rifaximin 200 mg three times a day, ciprofloxacin (500 mg two times a day and placebo once a day), or placebo three times a day for 3 days. Patients recorded in daily diaries the time and consistency of each stool and documented symptoms for 5 days after treatment. Stool samples were collected for microbiologic evaluations before and after treatment. The median time to last unformed stool (TLUS) in the Rifaximin group (32.0 hours) was less than one half that in the placebo group (65.5 hours; P = 0.001; risk ratio 1.6; 95% confidence interval 1.2, 2.2; primary efficacy endpoint). The median TLUS in the ciprofloxacin group was 28.8 hours (P = 0.0003 versus placebo; P = 0.35 versus Rifaximin). Rifaximin was less effective than ciprofloxacin for invasive intestinal bacterial pathogens. Oral Rifaximin is a safe and effective treatment of travelers' diarrhea caused by noninvasive pathogens.
-
Rifaximin a nonabsorbed oral antibiotic prevents shigellosis after experimental challenge
Clinical Infectious Diseases, 2006Co-Authors: David N. Taylor, Anna P Durbin, Robert Haake, Robin Mckenzie, Colleen Carpenter, Christophe B Atzinger, Louis A BourgeoisAbstract:BACKGROUND This double-blind, placebo-controlled study was conducted to assess the efficacy of the nonabsorbed oral antibiotic Rifaximin to prevent shigellosis in volunteers challenged with Shigella flexneri. METHODS Volunteers were randomized to receive either prophylactic Rifaximin (200 mg 3 times daily for 3 days; n = 15) or placebo (n = 10) on days 0, 1, and 2. On day 1, volunteers were challenged with approximately 1500 colony-forming units of S. flexneri 2a strain 2457T given orally in sodium bicarbonate buffer. RESULTS The incidence of diarrhea was 0 with Rifaximin, compared with 60% with placebo (P = .001). The median time to onset of diarrhea was 78.5 h with placebo (P < .001). The incidence of dysentery was 0 for Rifaximin and 10% for placebo (P = .4). The incidence of colonization with Shigella was 0 with Rifaximin, compared with 50% with placebo (P < .005). A significant serum or mucosal immune response after challenge by at least 1 indicator (immunoglobulin A titer, immunoglobulin G titer, and immunoglobulin A antibody-secreting cell count) was 0 with Rifaximin and 80% with placebo (P < .001). CONCLUSIONS Rifaximin was effective and well tolerated, compared with placebo, in preventing shigellosis in this double-blind study of volunteers challenged with S. flexneri 2a.
Zhi Dong Jiang - One of the best experts on this subject based on the ideXlab platform.
-
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
Antimicrobial Agents and Chemotherapy, 2013Co-Authors: Vishesh Kothary, Herbert L. Dupont, Zhi Dong Jiang, Ellen Scherl, Brian P Bosworth, Josee Harel, Kenneth W Simpson, Belgin DoganAbstract: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.
-
a randomized double blind placebo controlled pilot study to assess the ability of Rifaximin to prevent recurrent diarrhoea in patients with clostridium difficile infection
Journal of Antimicrobial Chemotherapy, 2011Co-Authors: Zhi Dong Jiang, Kevin W. Garey, Shashank S Ghantoji, Dhara N Shah, Musarat Habib, Vaneet Arora, Herbert L. DupontAbstract:BACKGROUND Uncontrolled case series have demonstrated decreased Clostridium difficile infection (CDI) recurrence in patients given Rifaximin after standard antibiotic therapy. However, clinical trials assessing whether Rifaximin decreases recurrent diarrhoea in patients with CDI have not been performed. The purpose of this study was to assess rates of recurrent diarrhoea in patients with CDI given Rifaximin versus placebo immediately after standard therapy. METHODS This was a randomized, double-blind, placebo-controlled pilot study. Patients with CDI and a Horn's index ≥1 were randomized to receive Rifaximin 400 mg three times daily or placebo for 20 days given immediately after finishing standard anti-CDI antibiotics. Patients were followed for 3 months and assessed for recurrent diarrhoea that included CDI recurrence (return of diarrhoea with a positive toxin test) and patient self-reported return of non-CDI diarrhoea after a period of wellness. RESULTS Sixty-eight patients aged 61 ± 18 years (50% male) were given Rifaximin (n = 33) or placebo (n = 35). Twenty-four of 68 (35%) patients had recurrent diarrhoea either due to recurrent CDI (23.5%) or self-reported diarrhoea (11.5%). Recurrent diarrhoea occurred in 17 of 35 (49%) patients given placebo and 7 of 33 (21%) given Rifaximin (P = 0.018). CDI recurrence occurred in 11 of 35 (31%) patients given placebo and 5 of 33 (15%) patients given Rifaximin (P = 0.11). Self-reported diarrhoea occurred in 6 of 35 (17%) of patients given placebo and 2 of 33 (6%) given Rifaximin (P = 0.15). CONCLUSIONS Patients with CDI given a Rifaximin chaser regimen experienced a decreased incidence of recurrent diarrhoea compared with placebo.
-
Bile Acids Improve the Antimicrobial Effect of Rifaximin
Antimicrobial agents and chemotherapy, 2010Co-Authors: Charles Darkoh, Zhi Dong Jiang, Lenard M. Lichtenberger, Nadim J. Ajami, Elizabeth J. Dial, Herbert L. DupontAbstract:Diarrhea is one of the most common infirmities affecting international travelers, occurring in 20 to 50% of persons from industrialized countries visiting developing regions. Enterotoxigenic Escherichia coli (ETEC) is the most common causative agent and is isolated from approximately half of the cases of traveler9s diarrhea. Rifaximin, a largely water-insoluble, nonabsorbable ( E. coli . However, the drug has minimal effect on the bacterial flora or the infecting E. coli strain in the aqueous environment of the colon. The purpose of the present study was to evaluate the antimicrobial effect and bioavailability of Rifaximin in aqueous solution in the presence and absence of physiologic concentrations of bile acids. The methods used included growth measurement of ETEC (strain H10407), Rifaximin solubility measurements, total bacterial protein determination, and assessment of the functional activity of Rifaximin by monitoring inhibition of bacterial β-galactosidase expression. Solubility studies showed Rifaximin to be 70- to 120-fold more soluble in bile acids (approximately 30% in 4 mM bile acids) than in aqueous solution. Addition of both purified bile acids and human bile to Rifaximin at subinhibitory and inhibitory concentrations significantly improved the drug9s anti-ETEC effect by 71% and 73%, respectively, after 4 h. This observation was confirmed by showing a decrease in the overall amount of total bacterial protein expressed during incubation of Rifaximin plus bile acids. Rifaximin-treated samples containing bile acids inhibited the expression of ETEC β-galactosidase at a higher magnitude than samples that did not contain bile acids. The study provides data showing that bile acids solubilize Rifaximin on a dose-response basis, increasing the drug9s bioavailability and antimicrobial effect. These observations suggest that Rifaximin may be more effective in the treatment of infections in the small intestine, due to the higher concentration of bile in this region of the gastrointestinal tract than in the colon. The water insolubility of Rifaximin is the likely explanation for the drug9s minimal effects on colonic flora and fecal pathogens, despite in vitro susceptibility.
-
Prevention of Travelers' Diarrhea With Rifaximin in US Travelers to Mexico
Journal of travel medicine, 2010Co-Authors: Francisco Martinez-sandoval, Zhi Dong Jiang, Pablo C. Okhuysen, Charles D. Ericsson, Enoch Bortey, William P Forbes, Juan H.m. Meléndez Romero, Norma Hernandez, Audrey L. Shaw, Herbert L. DupontAbstract:Background Because bacterial pathogens are the primary cause of travelers' diarrhea (TD), antibiotic prophylaxis is effective in TD prevention. This study assessed the efficacy and safety of the nonsystemic antibiotic Rifaximin in preventing TD in US travelers to Mexico. Methods Healthy adult students traveling to Mexico received Rifaximin 600 mg/d or placebo for 14 days and were followed for 7 days post‐treatment. Stool pattern and gastrointestinal symptoms were recorded in daily diary entries. The primary end point was prevention of TD during 14 days of treatment measured by time to first unformed stool. Results A total of 210 individuals received Rifaximin ( n = 106) or placebo ( n = 104) and were included in the safety population. Median age was 21 years (range, 18–75 y), and the majority of participants were female (65%). Efficacy analyses were conducted in a modified intent‐to‐treat population of 201 patients who received Rifaximin ( n = 99) or placebo ( n = 102). Rifaximin prophylaxis reduced risk of developing TD versus placebo ( p < 0.0001). A smaller percentage of individuals who received Rifaximin versus placebo developed all‐cause TD (20% vs 48%, respectively; p < 0.0001) or TD requiring antibiotic therapy (14% vs 32%, respectively; p = 0.003). More individuals in the Rifaximin group (76%) completed treatment without developing TD versus those in the placebo group (51%; p = 0.0004). Rifaximin provided a 58% protection rate against TD and was associated with fewer adverse events than placebo. Conclusions Prophylactic treatment with Rifaximin 600 mg/d for 14 days safely and effectively reduced the risk of developing TD in US travelers to Mexico. Rifaximin chemoprevention should be considered for TD in appropriate individuals traveling to high‐risk regions.
-
Rifaximin induced alteration of virulence of diarrhoea producing escherichia coli and shigella sonnei
International Journal of Antimicrobial Agents, 2010Co-Authors: Zhi Dong Jiang, Herbert L. DupontAbstract:Abstract Rifaximin shortens the duration of travellers' diarrhoea without important alteration of colonic flora. This study investigated the expression of virulence factors [heat-stable (ST) and heat-labile (LT) enterotoxins, surface adhesion factors (CS2/CS3, CS6) and matrix metalloproteinase-9 (MMP-9)] as well as the interleukin (IL)-8 induction potential of diarrhoeagenic Escherichia coli and Shigella sonnei strains exposed to Rifaximin (8, 32 and 64mg/L) for 4, 8, 18 and 24h. Following exposure to Rifaximin, enterotoxigenic E. coli (ETEC) isolates did not express ST/LT, CS2/CS3 or CS6, whereas enteroaggregative E. coli (EAEC) and S. sonnei isolates did not produce detectable amounts of MMP-9. Moreover, induction of IL-8 was undetectable. At subinhibitory concentrations, Rifaximin alters the virulence of ETEC, EAEC and S. sonnei isolates. These findings help explain the efficacy of Rifaximin despite minimal alteration of colonic flora.
Louis A Bourgeois - One of the best experts on this subject based on the ideXlab platform.
-
systemic pharmacokinetics of Rifaximin in volunteers with shigellosis
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: David N. Taylor, Anna P Durbin, Robert Haake, Robin Mckenzie, Colleen Carpenter, Louis A BourgeoisAbstract:Rifaximin is an oral antibiotic indicated for treatment of traveler's diarrhea. Rifaximin pharmacokinetics were evaluated in individuals challenged with Shigella flexneri. Peak plasma Rifaximin concentrations were low after nine consecutive doses, and no accumulation was observed. Rifaximin serum levels were minimal and similar to those previously reported in studies of healthy volunteers.
-
a randomized double blind multicenter study of Rifaximin compared with placebo and with ciprofloxacin in the treatment of travelers diarrhea
American Journal of Tropical Medicine and Hygiene, 2006Co-Authors: David N. Taylor, Robert Haake, Louis A Bourgeois, Zhi Dong Jiang, Charles D. Ericsson, Robert Steffen, Jane Halpern, Herbert L. DupontAbstract:Rifaximin was compared with placebo and ciprofloxacin for treatment of travelers' diarrhea in a randomized, double-blind clinical trial. Adult travelers (N = 399) consulting travel clinics in Mexico, Guatemala, and India were randomized to receive Rifaximin 200 mg three times a day, ciprofloxacin (500 mg two times a day and placebo once a day), or placebo three times a day for 3 days. Patients recorded in daily diaries the time and consistency of each stool and documented symptoms for 5 days after treatment. Stool samples were collected for microbiologic evaluations before and after treatment. The median time to last unformed stool (TLUS) in the Rifaximin group (32.0 hours) was less than one half that in the placebo group (65.5 hours; P = 0.001; risk ratio 1.6; 95% confidence interval 1.2, 2.2; primary efficacy endpoint). The median TLUS in the ciprofloxacin group was 28.8 hours (P = 0.0003 versus placebo; P = 0.35 versus Rifaximin). Rifaximin was less effective than ciprofloxacin for invasive intestinal bacterial pathogens. Oral Rifaximin is a safe and effective treatment of travelers' diarrhea caused by noninvasive pathogens.
-
Rifaximin a nonabsorbed oral antibiotic prevents shigellosis after experimental challenge
Clinical Infectious Diseases, 2006Co-Authors: David N. Taylor, Anna P Durbin, Robert Haake, Robin Mckenzie, Colleen Carpenter, Christophe B Atzinger, Louis A BourgeoisAbstract:BACKGROUND This double-blind, placebo-controlled study was conducted to assess the efficacy of the nonabsorbed oral antibiotic Rifaximin to prevent shigellosis in volunteers challenged with Shigella flexneri. METHODS Volunteers were randomized to receive either prophylactic Rifaximin (200 mg 3 times daily for 3 days; n = 15) or placebo (n = 10) on days 0, 1, and 2. On day 1, volunteers were challenged with approximately 1500 colony-forming units of S. flexneri 2a strain 2457T given orally in sodium bicarbonate buffer. RESULTS The incidence of diarrhea was 0 with Rifaximin, compared with 60% with placebo (P = .001). The median time to onset of diarrhea was 78.5 h with placebo (P < .001). The incidence of dysentery was 0 for Rifaximin and 10% for placebo (P = .4). The incidence of colonization with Shigella was 0 with Rifaximin, compared with 50% with placebo (P < .005). A significant serum or mucosal immune response after challenge by at least 1 indicator (immunoglobulin A titer, immunoglobulin G titer, and immunoglobulin A antibody-secreting cell count) was 0 with Rifaximin and 80% with placebo (P < .001). CONCLUSIONS Rifaximin was effective and well tolerated, compared with placebo, in preventing shigellosis in this double-blind study of volunteers challenged with S. flexneri 2a.
Mark Pimentel - One of the best experts on this subject based on the ideXlab platform.
-
Rifaximin is associated with modest transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea predominant irritable bowel syndrome
Gut microbes, 2019Co-Authors: Anthony A Fodor, Mark Pimentel, Anthony Lembo, William D Chey, Pamela L Golden, Robert J Israel, Ian M CarrollAbstract:Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of Rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label Rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of Rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label Rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of Rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that Rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by Rifaximin are causally linked to IBS-D. ClinicalTrials.gov identifier number: NCT01543178.
-
repeat treatment with Rifaximin is safe and effective in patients with diarrhea predominant irritable bowel syndrome
Gastroenterology, 2016Co-Authors: Anthony Lembo, Enoch Bortey, Mark Pimentel, Philip Schoenfeld, Craig Paterson, Satish S C Rao, Brooks D Cash, Leonard B Weinstock, William P ForbesAbstract:Background & Aims Few treatments have demonstrated efficacy and safety for diarrhea-predominant irritable bowel syndrome (IBS-D). A phase 3, randomized, double-blind, placebo-controlled trial was performed to evaluate the safety and efficacy of repeat treatment with the nonsystemic antibiotic Rifaximin. Methods The trial included adults with IBS-D, mean abdominal pain and bloating scores of 3 or more, and loose stool, located at 270 centers in the United States and Europe from February 2012 through June 2014. Those responding to a 2-week course of open-label Rifaximin 550 mg 3 times daily, who then relapsed during an observation phase (up to 18 weeks), were randomly assigned to groups given repeat treatments of Rifaximin 550 mg or placebo 3 times daily for 2 weeks. The primary end point was percentage of responders after first repeat treatment, defined as a decrease in abdominal pain of ≥30% from baseline and a decrease in frequency of loose stools of ≥50% from baseline, for 2 or more weeks during a 4-week post-treatment period. Results Of 1074 patients (44.1%) who responded to open-label Rifaximin, 382 (35.6%) did not relapse and 692 (64.4%) did; of these, 636 were randomly assigned to receive repeat treatment with Rifaximin (n = 328) or placebo (n = 308). The percentage of responders was significantly greater with Rifaximin than placebo (38.1% vs 31.5%; P = .03). The percentage of responders for abdominal pain (50.6% vs 42.2%; P = .018) was significantly greater with Rifaximin than placebo, but not stool consistency (51.8% vs 50.0%; P = .42). Significant improvements were also noted for prevention of recurrence, durable response, and bowel movement urgency. Adverse event rates were low and similar between groups. Conclusions In a phase 3 study of patients with relapsing symptoms of IBS-D, repeat Rifaximin treatment was efficacious and well tolerated. ClinicalTrials.gov ID: NCT01543178.
-
safety and tolerability of Rifaximin for the treatment of irritable bowel syndrome without constipation a pooled analysis of randomised double blind placebo controlled trials
Alimentary Pharmacology & Therapeutics, 2014Co-Authors: Philip Schoenfeld, Enoch Bortey, Mark Pimentel, Anthony Lembo, Lin Chang, William D Chey, Craig Paterson, William P ForbesAbstract:Summary Background The efficacy of Rifaximin, a nonsystemic, gut-targeted antibiotic for reducing non–constipation-predominant irritable bowel syndrome (non-C IBS) symptoms, has been demonstrated in one phase 2b and two phase 3 randomised, double-blind, placebo-controlled trials, but detailed data about Rifaximin safety and tolerability during treatment and subsequent follow-up periods are lacking. Aim To assess and determine the frequency of Rifaximin and placebo adverse events (AEs) in phase 2b and phase 3 non-C IBS trials. Methods A post hoc pooled safety analysis of the phase 2b (Rifaximin 275, 550, and 1100 mg twice daily for 2 weeks; 550 mg twice daily for 4 weeks) and phase 3 (Rifaximin 550 mg three times daily for 2 weeks) studies was performed. Data on treatment and post-treatment AEs were collected. Patients were followed up for 12 weeks and 10 weeks post-treatment in the phase 2b and phase 3 trials, respectively. Results Patients receiving Rifaximin (n = 1103) and placebo (n = 829) had a similar incidence of drug-related AEs (12.1% vs. 10.7%), serious AEs (1.5% vs. 2.2%), drug-related AEs resulting in study discontinuation (0.8% vs. 0.8%), gastrointestinal-associated AEs (12.2% vs. 12.2%) and infection-associated AEs (8.5% vs. 9.5%). There were no cases of Clostridium difficile colitis or deaths. Conclusions The safety and tolerability profile of Rifaximin during treatment and post-treatment was comparable to placebo. Future research should define the safety and tolerability profile, including risk of C. difficile colitis and microbial antibiotic resistance, with repeated courses of Rifaximin in patients with non—constipation-predominant irritable bowel syndrome (ClinicalTrials.gov: NCT00269412, NCT00731679, and NCT00724126).
-
The Effect of Rifaximin on Gut Flora and Staphylococcus Resistance
Digestive diseases and sciences, 2013Co-Authors: Mi-sung Kim, Walter Morales, Andres Ardila Hani, Sharon Kim, Gene Kim, Stacy Weitsman, Christopher Chang, Mark PimentelAbstract:Aim 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.
-
Review of Rifaximin as treatment for SIBO and IBS
Expert opinion on investigational drugs, 2009Co-Authors: Mark PimentelAbstract:Background: Rifaximin is a broad-range, gastrointestinal-specific antibiotic that demonstrates no clinically relevant bacterial resistance. Therefore, Rifaximin may be useful in the treatment of gastrointestinal disorders associated with altered bacterial flora, including irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). Objective: To review Rifaximin for treatment of IBS and SIBO. Methods: Review of Rifaximin clinical trials. Results/conclusion: Rifaximin improved global symptoms in 33 – 92% of patients and eradicated SIBO in up to 84% of patients with IBS, with results sustained up to 10 weeks post-treatment. Rifaximin caused a lower number of adverse events compared with metronidazole or levofloxacin and may have a more favorable adverse event profile than systemic antibiotics, without clinically relevant antibiotic resistance.
