Rifaximin Use Research Articles

Pharmacokinetic drug evaluation of rifaximin for treatment of diarrhea-predominant irritable bowel syndrome

ABSTRACTIntroduction: Rifaximin is a poorly absorbable antibiotic with a broad-spectrum activity against both Gram-negative and -positive bacteria. It is active in the small intestine due to its high bile solubility, whereas in the aqueous environment of the colon, it shows limited efficacy against highly susceptible bacteria. These unique pharmacokinetic properties limit its systemic effects and can correct gut microflora imbalances. Thus, rifaximin has become a major therapeutic agent in several gastrointestinal diseases in which an imbalance in gut microflora may play a role, including diarrhea predominant irritable bowel syndrome (IBS-D).Area covered: This is an up-to-date review focusing on the efficacy of rifaximin in the treatment of IBS-D in both adult and pediatric populations. We will review the pharmacokinetic properties of rifaximin, including its absorption in health and disease, mechanisms of action, and interactions with other drugs.Expert opinion: Given its safety profile and its negligible absorption, rifaximin is a suitable treatment for IBS-D, in both adults and children. The possibility of modulating gut microbiota composition without side effects has made this drug an appealing therapeutic agent in highly prevalent gastrointestinal diseases. However, to date, monitoring for the development of resistant bacterial strains during long-term rifaximin use is still lacking.

NON-ANTIBIOTIC USE OF ANTIBIOTICS

Abstract Antibiotics are widely used medicines in the treatment of infectious diseases. However, some of them show also non-antibiotic properties, which are increasingly used in the treatment of non-infectious diseases. The authors of this publication believe that this is one of the reasons behind antibiotic dissemination in the environment and, ipso facto, behind the increasing risk of bacterial resistance. It is worth remembering that, along with the progress in science and better knowledge of the new properties of antibiotics, every extension of indications for antimicrobial agents may restrict their primary indications. Progress in science does not always mean progress in therapy. In fact, it may sometimes have an opposite effect and we should be able to assess the benefit/risk ratio. The aim of this study was to present other than antibacterial properties of antibiotics which currently are or may be used in the future in the treatment of non-infectious diseases, as well as to assess the long-term effects of extending the indications for medicines commonly used in the treatment of infectious diseases. To the best of the authors’ knowledge, such attempt has not been made so far, therefore authors decided to review the most important, useful or promising reports on non-antibiotic use of antibiotics. The article summarizes the latest data on prokinetic action of erythromycin, anti-inflammatory and immunomodulatory action of azithromycine, potential use of doxycycline as an anticancer and anti-inflammatory agent, and also anti-inflammatory, neuroprotective, antioxidant and antiapoptotic properties of minocycline. Futhermore, the basics of demeclocycline application in the treatment of inappropriate antidiuretic hormone hypesecretion syndrome and rifaximin use as an anti-inflammatory and eubiotic agent are presented. Neuroprotective action of ceftriaxone and anti-inflammatory and immunostimulatory action of fusafungine were also described. 1. Introduction – antibiotics as potentially effective agents in the therapy of non-infectious diseases. 2. Erythromycine – prokinetic action. 3. Azithromycine – anti-inflammatory and immunomodulatory action. 4. Doxycycline – anticancer and anti-inflammatory action. 5. Minocycline – anti-inflammatory, neuroprotective, antioxidant and antiapoptotic action. 6. Demeclocycline – inhibition of the antiantidiuretic hormone action. 7. Rifaximin – anti-inflammatory action / eubiotic. 8. Ceftriaxone – neuroprotective action. 9. Fusafungine – anti-inflammatory and immunostimulatory action. 10. Summary

The Prevalence of Depression in Small Intestinal Bacterial Overgrowth

Introduction: Many patients who seek care for gastrointestinal symptoms have an associated affective disorder. Gastrointestinal diseases including food allergies, H. Pylori infection, irritable bowel syndrome (IBS), and small intestinal bacterial overgrowth, have all been shown to have an increased probability of depression. The gastrointestinal disease most widely studied in its association with psychiatric disease is irritable bowel syndrome (IBS). There is significant overlap between irritable bowel syndrome and small intestinal bacterial overgrowth (SIBO). The prevalence of SIBO in patients meeting Rome II criteria for IBS was 4-64%. Moreover, ninety-two percent of patients with IBS complain of bloating and abdominal pain, which are also symptoms of SIBO. Thus, we hypothesize that patients with small intestinal bacterial overgrowth will have an increased prevalence of depression as compared to the general population. Methods: 67 subjects were referred for hydrogen breath test to evaluate for small intestinal bacterial overgrowth at Montefiore Medical Center. Data was collected from July 2016 to May 2017. 15 patients were excluded from the study because of: previous treatment of small intestinal bacterial overgrowth, prior rifaximin use, prior gastrointestinal surgery, prior gastrointestinal cancer, or pregnancy. The remaining 52 were provided with validated depression (Patient Health Questionnaire 9) and anxiety (Generalized Anxiety Disorder 7) surveys. Results: Subjects were on average 54 years old, 83% of minority race, 63% female, 37% obese, and 42% had a prior history of depression. Mean Patient Health Questionnaire-9 (PHQ-9) score was 7, with 46% meeting criteria for depression. Thirty patients (58%) tested positive and twenty-two patients (42%) tested negative for small intestinal bacterial growth by hydrogen breath test. Of the patients who tested positive for SIBO, 15 (50%) tested positive for depression and 11 (37%) tested positive for anxiety. Of the patients who tested negative for SIBO, 9 (41%) tested positive for depression and 7 (32%) tested positive for anxiety. There was no significant difference in rate of depression between the SIBO positive and negative cohorts. Conclusion: Although patients with small intestinal bacterial overgrowth had more depression and anxiety in this study, this was not found to be of statistical significance.

A meta-analysis of the use of rifaximin to prevent travellers' diarrhoea.

Travellers' diarrhoea affects tens of millions of people travelling to less developed countries or regions annually. There are positive reports of the use of rifaximin, a non-absorbed, gut-selective antibiotic to prevent travellers' diarrhoea. This study will critically review and analyse clinical trials on the subject. Using the keywords [diarrhoea OR diarrhoea OR travel*] AND [rifaximin OR xifaxan OR xifaxanta OR normix OR rifagut], a preliminary search on the PubMed and Ovid databases yielded 411 papers published in English between 1 January 1988 and 1 July 2016. Of these, there were only five relevant clinical trials. The clinical trials were double-blind, placebo-controlled, randomized trials with a total of 879 subjects. The meta-analysis found significant reduction in risk of travellers' diarrhoea with rifaximin use compared to placebo (pooled RR 0.478, 95% CI: 0.375-0.610, and P < 0.001). For the entire travel and follow-up period, the risk of developing travellers' diarrhoea was significantly greater in individuals receiving the placebo than those receiving rifaximin (daily doses of 400-600 mg). Overall, rifaximin offered significant protection rates of 48-72%, with lower protection rates for Asian than Latin American countries. In terms of tolerability, similar rates of adverse events were reported for the rifaximin and placebo group ( P > 0.05), with no clinically significant or serious adverse events related to rifaximin use. There is good evidence supporting the use of rifaximin as a chemoprophylactic agent against travellers' diarrhoea, especially in individuals who are at high risk of severe complications from acute infectious diarrhoea. Rifaximin has an excellent tolerability/safety profile and demonstrated efficacy against diarrhoeagenic Escherichia coli and even enteroinvasive bacteria such Campylobacter species. Future studies should study the most effective dosing regimen for rifaximin chemoprophylaxis, as well as profile local antimicrobial resistance/susceptibility data in less developed regions to further guide rifaximin use.

Age-related Morbidity and Mortality After Transjugular Intrahepatic Portosystemic Shunts

To compare age-related morbidity and mortality after transjugular intrahepatic portosystemic shunts (TIPS). We performed a retrospective chart review of patients who underwent TIPS at the University of California Los Angeles Medical Center between 2008 to 2014. Elderly patients (65 y and older) were matched with nonelderly patients (controls, below 65 y) by model for end-stage liver disease (MELD) score (±3), indication for TIPS (refractory ascites vs. variceal bleeding), serum sodium level (±5), in a ratio of 1:1. Endpoints measures were hospital stay post-TIPS, rifaximin, or lactulose use, TIPS failure at 30 days, readmission at 90 days, MELD at 90 days, and mortality at 90 days. A total of 30 patient matches were included in this study: 30 control and 30 elderly patients. The median [interquartile (IQR)] MELD scores for controls and elderly were 11 (9, 13.8) for the controls and 11.5 (9, 14.8) for elderly patients (P=0.139). There were no significant differences in serum sodium and indication for TIPS. Thirty and 90-day follow-up laboratory test results were also similar between elderly and control patients. Event-free survival at 90 days was similar between controls and elderly patients [odds ratio (OR), 0.86; 95% confidence interval (CI), 0.3-2.5; P>0.05]. There was a trend toward greater hospitalization (OR, 1.76; 95% CI, 0.52-5.95; P=0.546) and mortality (OR, 3.3; 95% CI, 0.3-14.01; P=0.182). The results of this study suggest event-free survival is similar between nonelderly and elderly patients. Although statistically significant, there is a tendency toward greater mortality and hospitalization in the elderly.

Rifaximin and diverticular disease: Position paper of the Italian Society of Gastroenterology (SIGE)

Management of diverticular disease has significantly improved in the last decade. Antibiotic treatment is used for symptom relief and prevention of complications. In Italy, the non-absorbable antibiotic rifaximin is one of the most frequently used drugs, and it is perceived as the reference drug to treat symptomatic diverticular disease. Its non-systemic absorption and high faecal concentrations have oriented rifaximin use to the gastrointestinal tract, where rifaximin exerts eubiotic effects representing an additional value to its antibiotic activity. This position paper was commissioned by the Italian Society of Gastroenterology governing board for a panel of experts (RC, GB, BA) to highlight the indications for treatment of diverticular disease. There is a lack of rationale for drug use for the primary prevention of diverticulitis in patients with diverticulosis; thus, rifaximin use should be avoided. The cyclic use of rifaximin, in association with high-fibre intake, is safe and useful for the treatment of symptomatic uncomplicated diverticular disease, even if the cost-efficacy of long-term treatment remains to be determined. The use of rifaximin in the prevention of diverticulitis recurrence is promising, but the low therapeutic advantage needs to be verified. No evidence is available on the efficacy of rifaximin treatment on acute uncomplicated diverticulitis.

Multi-Drug-resistant Organism (MDRO) Infections in Liver Transplant Recipients 30 Days Post-Transplant

BackgroundThe leading cause of morbidity and mortality in liver transplant recipients (LTR) is bacterial infection, with the highest rates seen in the first 30 days after transplantation. LTR may be at increased risk for MDROs due to their complicated pre- and post- transplantation course.MethodsWe performed a retrospective chart review of the clinical characteristics of LTR to determine risk factors for the development of MDROs post transplantation. A secondary analysis was performed to determine the role of Rifaximin in the development of MDRO infections given its known antimicrobial properties. All adult, first time LTR (January 2012 to December 2016) were included in this study. We determined relative risk for specific clinical characteristics by performing a univariate analysis.ResultsOf the 329 adult LTR, 92 (27.9%) developed a bacterial infection and 36 (11%) developed MDRO infections in the immediate post-operative period; MDROs accounted for 39.1% (36/92) of all infections. The majority of MDRO infections were due to gram-negative rods (62%). However, the most common isolates were: Vancomycin-Resistant Enterococci (23.8%) and Klebsiella pneumoniae(19%). The most common sites of infection were: respiratory tract (32%), urine (23%), and intraabdominal (20%). The following pre transplant risk factors for the development of an MDRO infection included: prior antibiotic treatment and ICU admission (P < 0.05). However, spontaneous bacterial peritonitis (SBP) prophylaxis alone was not associated with an increased risk for an MDRO infection. Post transplant risk factors for the development of an MDRO infection included: prolonged ICU stay, return to the OR, renal replacement therapy, and mechanical ventilation (P < 0.05). Rifaximin use was associated with a relative risk of 2.2 (P = 0.0198) for the development of an MDRO infection. In patients who had received Rifaximin, the MELD score of those who developed MDRO infections was higher at 28 vs. those who did not develop an MDRO infection at 23 (P = 0.017).ConclusionNearly 40% of LTR who develop post-operative infections are due to MDROs with antibiotic exposure and post-transplant critical care complications as contributing factors. Pre-transplant Rifaximin use may be associated with the development of MDRO infections in LTR.Disclosures All authors: No reported disclosures.

Epilepsy as a risk factor for hepatic encephalopathy in patients with cirrhosis: a cohort study.

BackgroundEpilepsy is associated with an increased mortality among cirrhosis patients, but the reasons are unknown. We aimed to determine whether epilepsy is a risk factor for developing hepatic encephalopathy (HE), which is a strong predictor of mortality.MethodsWe used data from three randomized 1-year trials of satavaptan in cirrhosis patients with ascites. With Cox regression, we compared the hazard rates of HE grade 1–4 between those cirrhosis patients who did or did not have epilepsy. We adjusted for confounding by gender, age, cirrhosis etiology, diabetes, history of HE, Model for Endstage Liver Disease (MELD) score, serum sodium, albumin, lactulose use, rifaximin use, and benzodiazepine/barbiturate sedation. In a supplementary analysis we examined the association between epilepsy and the hazard rate of HE grade 2–4.ResultsOf the 1120 cirrhosis patients with ascites, 21 (1.9 %) were diagnosed with epilepsy. These patients had better liver function at inclusion than the patients without epilepsy (median MELD score 7.9 vs. 11.4), and only one died during the trials. Nevertheless, seven patients with epilepsy had an HE episode during the follow-up, and the adjusted hazard ratio of HE grade 1–4 for patients with epilepsy vs. controls was 2.12 (95 % CI 0.99–4.55). The corresponding hazard ratio of HE grade 2–4 was 3.83 (95 % CI 1.65–8.87).ConclusionsOur findings suggest that epilepsy is associated with an increased risk of HE in patients with cirrhosis.

The International Liver Congress (ILC) 2016: Rifaximin Use in Cirrhosis-Related Hepatological Disorders and New Perspectives

Rifaximin (RFX)-α is a broad-spectrum antibiotic that targets commensal gut bacteria and reduces the excess ammonia produced by the gut bacteria of patients with cirrhosis. This innovative agent has been approved in most European countries for several therapeutic indications, including the prevention of episodes of overt hepatic encephalopathy (HE) in adult patients. New data on RFX use in HE were presented at the International Liver Congress (ILC), namely the annual meeting of the European Association for the Study of the Liver (EASL) held in Barcelona, Spain, from 13th–17th April 2016. The beneficial effects of RFX have been attributed to the antibiotic action against a broad spectrum of gut bacteria, accompanied by the advantage of its very poor systemic absorption generating a gastrointestinal tropism. More recently, data are accumulating to suggest that other non-antibacterial effects contribute to RFX efficacy, making it a very interesting option for enteric diseases. RFX is thus explored outside of HE, in both cirrhotic and non-cirrhotic patients. This review aims to highlight the presentations from ILC 2016 focussing on RFX developments in clinical research.

Management of Hepatic Encephalopathy: A Primer.

To review the management of hepatic encephalopathy (HE), including lifestyle modifying strategies and pharmacological interventions. A literature search of PubMed through March 2016 was conducted utilizing the keywords hepatic encephalopathy, ammonia, and cirrhosis All published articles evaluating treatments for HE were considered. Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of HE in humans were reviewed; relevant clinical data were selected and included. HE is a prevalent complication of portal hypertension and cirrhosis that results in altered mental status and neuropsychiatric impairment. Although the pathogenesis has not been elucidated, numerous treatment options exist. This review will explore the role of dietary interventions and supplements, including use of zinc, acetyl-l-carnitine, and probiotics, in the management of HE. Additionally, the use of various ammonia-lowering agents will be evaluated. The nonabsorbable disaccharides represent first-line therapies for the management and prophylaxis of HE; rifaximin use has been demonstrated to be effective for both treatment and prophylaxis of HE symptoms, with use relegated to those patients who fail to respond to or tolerate the nonabsorbable disaccharides. In light of toxicities associated with the use of neomycin and metronidazole, recent guidelines recommend both as alternatives for the treatment of HE, with the use of vancomycin discouraged. Although numerous treatment options are available, management of HE remains a clinical challenge. Additional research is needed to explore the pathogenesis and better understand the role of pharmacotherapy in managing this condition.

The clinical and molecular epidemiology of pre-transplant vancomycin-resistant enterococci colonization among liver transplant recipients.

Vancomycin-resistant enterococci (VRE) infections cause significant morbidity in liver transplant recipients. The epidemiology and impact of pre-transplant colonization with VRE among patients who undergo liver transplantation are poorly understood. We conducted an observational cohort study to identify risk factors and outcomes associated with pre-transplant VRE colonization and described the molecular diversity among VRE strains colonizing patients who undergo liver transplantation. Perirectal VRE surveillance cultures were performed prior to transplantation. Repetitive sequence-based polymerase chain reaction (rep-PCR) testing was used to identify clonality among VRE isolates. Of 61 patients who underwent pre-transplant VRE surveillance and subsequent liver transplantation, 27 (44%) were colonized with VRE. In multivariate analysis, pre-transplant VRE colonization was associated with central venous catheterization (OR 9.4, 95% confidence interval [CI]= 1.3-70.2, p = 0.03) and rifaximin use (OR 15.4, 95% CI 1.5-159.7, p = 0.02). Pre-transplant VRE colonization was associated with more hospital days post-transplant (26.6 vs. 16.1 d, p = 0.04). Of VRE-colonized patients analyzed with rep-PCR, 68% were colonized with the same strain as another patient in the cohort. Active surveillance identifies VRE-colonized patients who may benefit from targeted antimicrobial prophylaxis and enhanced infection prevention measures to prevent VRE spread. The relationship between rifaximin receipt and VRE colonization warrants further study. The identification of similar VRE isolates may suggest linked transmission during pre-transplant hospitalizations, which should be further investigated in prospective studies.

Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea.

The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin). To review the literature regarding the role of rifaximin in IBS and its potential mechanism(s) of action. A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'. Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO. Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS.

Chronic Rifaximin (Rfx) Use in Cirrhotic Patients Is Associated With Decreased Rate of C. difficile Infection (CDI)

Chronic Rifaximin (Rfx) Use in Cirrhotic Patients Is Associated With Decreased Rate of C. difficile Infection (CDI)

Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286.

Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4(+) T-cell counts <350 cells/mm(3) were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8(+)T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8(+)T-cell activation. Trial registration number. NCT01466595.

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

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.

Tu1076 Predictive Value of Adequate Relief of Global IBS Symptoms During First Two Weeks of Rifaximin use on Subsequent Relief of Daily IBS Symptoms and Daily Bloating Symptoms

Tu1076 Predictive Value of Adequate Relief of Global IBS Symptoms During First Two Weeks of Rifaximin use on Subsequent Relief of Daily IBS Symptoms and Daily Bloating Symptoms

169 Markers of Bacterial Translocation in Patients With Chronic Liver Disease

G A A b st ra ct s for HE-related, and all-cause hospitalizations were 0.21 and 0.45 with long term rifaximin use; both rates were significantly lower (p<0.0001, p=0.0051) compared to the corresponding rates for RCT placebo (0.72, 1.31). Safety was not adversely impacted with increased long term rifaximin exposure. Adverse event rates and the rate of change in the mean MELD scores remained stable in the long term. Mortality rates with long term rifaximin exposure were similar between all rifaximin patients (0.1) and the RCT placebo group (0.2) . Conclusions: Long term treatment with rifaximin 550 mg BID afforded continued protection from HE, reduced the hospitalization rate, and did not adversely affect safety or mortality in patients with cirrhosis.

Mo1765 High Level Rifaximin Resistance in Escherichia coli Associated With Inflammatory Bowel Disease Correlates With Prior Rifaximin use and Mutations in Rpob

Mo1765 High Level Rifaximin Resistance in Escherichia coli Associated With Inflammatory Bowel Disease Correlates With Prior Rifaximin use and Mutations in Rpob

Impact of rifaximin use for hepatic encephalopathy on the risk of early post‐transplant infections in liver transplant recipients

Whether the use of rifaximin for hepatic encephalopathy during liver transplant candidacy has an impact on post-transplant infections is not known. We compared the frequency and spectrum of infections within 90 d post-transplant in liver transplant recipients who did and did not receive rifaximin for hepatic encephalopathy during transplant candidacy. Of 110 consecutive liver transplant recipients, 30 (27%) received rifaximin. Rifaximin users were more severely ill based on higher Model for End-Stage Liver Disease (MELD) score (p=0.005). When controlled for MELD (stratified by MELD<30, MELD≥30), the risk of infections was significantly lower in rifaximin vs. no rifaximin recipients (OR=0.269, 95% CI 0.078-0.0.934, p=0.026). Rifaximin use was not associated with a higher risk of multidrug resistant bacterial infections (OR=1.8, 95% CI 0.42-8.35, p=0.40). The probability of post-transplant survival at 90 d did not differ for patients with or without rifaximin use (0.90 for both groups, p=0.56). Rifaximin appeared to have a protective effect against early post-transplant infections in more severely ill liver transplant recipients. Rifaximin use did not select for multidrug resistant bacteria in these patients.

Rifaximin for the treatment of irritable bowel syndrome

Introduction: Few therapeutic options are available for irritable bowel syndrome (IBS). Lubiprostone is approved by the FDA for IBS with constipation, and alosetron in IBS with diarrhea (IBS-D). It has been proposed that alterations in the bowel microflora may play a role in the pathophysiology of IBS, and that modulation of the microflora holds therapeutic potential. Rifaximin is a nonsystemic antibiotic that has shown efficacy in IBS.Areas covered: This narrative review covers the treatment options available for IBS-D and focuses on rifaximin. Rifaximin pharmacodynamics, clinical pharmacology and results of clinical studies from proof of concept to the latest Phase III and retreatment studies in IBS are summarized. Challenges to rifaximin use, safety issues and regulatory data are also discussed.Expert opinion: The evidence supports rifaximin as an emerging treatment for IBS. Strategies for appropriate patient selection need to be further developed, and continued efficacy of rifaximin over repeated treatment courses needs to be better characterized.