Rifaximin Use Research Articles

Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin.

Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health1. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action2, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease3, causes cross-resistance to daptomycin in VREfm. Amino acid changes arising within the bacterial RNA polymerase in response to rifaximin exposure cause upregulation of a previously uncharacterized operon (prdRAB) that leads to cell membrane remodelling and cross-resistance to daptomycin through reduced binding of the antibiotic. VREfm with these mutations are spread globally, making this a major mechanism of resistance. Rifaximin has been considered 'low risk' for the development of antibiotic resistance. Our study shows that this assumption is flawed and that widespread rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin, a major last-resort intervention for multidrug-resistant pathogens. These findings demonstrate how unanticipated antibiotic cross-resistance can undermine global strategies designed to preserve the clinical use of critical antibiotics.

S1704 Impact of Rifaximin Use on Overt Hepatic Encephalopathy (OHE) Rehospitalizations Post-Discharge From an OHE Hospitalization in Commercially and Medicare-Insured Patients

S1704 Impact of Rifaximin Use on Overt Hepatic Encephalopathy (OHE) Rehospitalizations Post-Discharge From an OHE Hospitalization in Commercially and Medicare-Insured Patients

The role of pharmaceutical care in the use of rifaximin for the treatment of diarrhea

the management of diarrhea represents a prevalent issue within the realm of healthcare. Rifaximin is recommended to treat traveler's diarrhea and irritable bowel syndrome. At the same time, it is important to rationally use an antimicrobial drug to prevent the development of antimicrobial resistance. Aim: to evaluate the role of pharmaceutical care in using rifaximin to treat diarrhea, based on a questionnaire. A questionnaire survey was done among 55 pharmacy professionals and 42 pharmacy visitors regarding the dispensing and use of rifaximin for diarrhea treatment. The survey of pharmacy visitors revealed that rifaximin was used for the treatment of small intestinal bacterial overgrowth syndrome (32 cases), traveler's diarrhea (7 cases), and irritable bowel syndrome with diarrhea (3 cases). Patients did not undergo stool culture before rifaximin prescription, which could have prevented antimicrobial resistance and ruled out other causes of diarrhea. It was found that 14% of respondents reported improvement the next day, while 83.3% reported improvement within three days. Pharmacists can educate visitors about the importance of completing the treatment course. Five percent of respondents reported nausea as an adverse reaction. Pharmacists dispensed rifaximin for the treatment of diarrhea in adults almost three times more often than in children. The tablet form of the drug was used in 94.5% of cases, while the oral suspension was used in 5.5% of cases. The majority of pharmacy visitors (89.0%) received rifaximin with a doctor's prescription, and 10.9% without a prescription, which emphasizes the importance of pharmaceutical care to prevent irrational use of the drug. The results of the study show that 92.7% of pharmacists provide recommendations on the safety of rifaximin use, and 78.2% recommend abstaining from alcohol during treatment. Only 21.8% of pharmacists warn about the possible staining of urine, which can cause concern for patients. The majority of pharmacists (89.1%) systematically ask women about possible pregnancy, which indicates their awareness of safe pharmacotherapy. Pharmacists also clarify the simultaneous use of rifaximin with other drugs: 32.7% ask about taking oral contraceptives, 7.3% – antiarrhythmic drugs, and 3.6% – warfarin. mailto:https://meshb.nlm.nih.gov/record/ui?ui=D002648Pharmacists can enhance the effectiveness of rifaximin treatment by preventing its uncontrolled use, emphasizing the importance of completing the treatment course and informing about possible adverse reactions. When providing pharmaceutical care to visitors taking rifaximin, pharmacists should educate them about potential changes in urine color. Additionally, pharmaceutical workers advise women taking oral contraceptives to use additional contraceptive methods while taking rifaximin.

Single nuclear RNA sequencing of terminal ileum in patients with cirrhosis demonstrates multi-faceted alterations in the intestinal barrier

Patients with cirrhosis have intestinal barrier dysfunction but the role of the individual cell types in human small intestine is unclear. We performed single-nuclear RNA sequencing (snRNAseq) in the pinch biopsies of terminal ileum of four age-matched men [56 years, healthy control, compensated, early (ascites and lactulose use) and advanced decompensated cirrhosis (ascites and rifaximin use)]. Cell type proportions, differential gene expressions, cell-type specific pathway analysis using IPA, and cellular crosstalk dynamics were compared. Stem cells, enterocytes and Paneth cells were lowest in advanced decompensation. Immune cells like naive CD4 + T cells were lowest while ITGAE + cells were highest in advanced decompensation patients. MECOM had lowest expression in stem cells in advanced decompensation. Defensin and mucin sulfation gene (PAPSS2) which can stabilize the mucus barrier expression were lowest while IL1, IL6 and TNF-related genes were significantly upregulated in the enterocytes, goblet, and Paneth cells in decompensated subjects. IPA analysis showed higher inflammatory pathways in enterocytes, stem, goblet, and Paneth cells in decompensated patients. Cellular crosstalk analysis showed that desmosome, protease-activated receptors, and cadherin-catenin complex interactions were most perturbed in decompensated patients. In summary, the snRNAseq of the human terminal ileum in 4 subjects (1 control and three cirrhosis) identified multidimensional alteration in the intestinal barrier with lower stem cells and altered gene expression focused on inflammation, mucin sulfation and cell–cell interactions with cirrhosis decompensation.

Impact of rifaximin use in infections and mortality in patients with decompensated cirrhosis and hepatic encephalopathy.

Infections in patients with cirrhosis are associated with high morbidity and mortality. Rifaximin is an antibiotic used to treat and prevent hepatic encephalopathy (HE); however, it has been suggested that it may play a crucial role in reducing infections in these populations. To evaluate the role of rifaximin in preventing frequent cirrhosis-related infections [spontaneous bacterial peritonitis, pneumonia, urinary tract infection (UTI), and bacteremia], Clostridioides difficile infection, and all-cause mortality, as well as determining adverse effects and adherence to the drug. A retrospective cohort study was conducted on decompensated cirrhotic patients with history of HE between January 2017 and November 2022 at a university center. Patients with cirrhosis, regardless of their etiology and severity, were included in the study, encompassing both hospitalized and outpatient cases. The statistical analysis included adjusted general linear models, Poisson regressions, and propensity score matching. We included 153 patients. The mean age in the cohort was 60.2 ± 12.3 years and 67 (43.8%) were women. The main cause of cirrhosis was metabolic dysfunction-associated steatotic liver disease 52 (38%), and the median Model of End-Stage Liver Disease sodium was 16.5 (7-32). In the cohort, 65 (45%) patients used rifaximin. The mean follow-up was 32 months. Eighty-five patients with infectious events were recorded, and a total of 164 infectious events were registered. The main infectious events were UTIs (62, 37.8%) and pneumonia (38, 23.2%). The use of rifaximin was associated with lower infection rates, displaying an incidence rate ratio (IRR) of 0.64 [95% confidence interval (CI) (0.47-0.89); p = 0.008]. However, no discernible impact on mortality outcome was observed [IRR 1.9, 95% CI (0.9-4.0); p = 0.09]. There were no reported adverse effects, and no patient discontinued the therapy due to adverse effects. The use of rifaximin significantly reduces infections in patients with cirrhosis and HE. Despite rifaximin was associated with a decreased all-cause mortality, this impact was not statistically significant in the adjusted analysis.

Impact of rifaximin use following an initial overt hepatic encephalopathy hospitalization on rehospitalization and costs

AimTo assess the impact of rifaximin (± lactulose) use following discharge of an initial overt hepatic encephalopathy (OHE) hospitalization on OHE rehospitalizations and healthcare costs in a real-world setting.MethodsAdults (18–64 years) with an OHE hospitalization were identified from MarketScan® Commercial claims (Q4′15–Q2′20), classified into two mutually exclusive treatment cohorts (i.e. rifaximin and no rifaximin treatment), and further stratified into four subgroups based on decreasing quality of care (QoC; i.e. Type 1 – rifaximin without delay post-discharge; Type 2 – rifaximin with delay post-discharge; Type 3 – lactulose only post-discharge; Type 4 – no rifaximin/lactulose treatment post-discharge). The impact of rifaximin use on 30-day and annualized OHE hospitalizations and healthcare costs were assessed between cohorts and by the QoC subgroup.ResultsCharacteristics were similar between the rifaximin (N = 1,452; Type 1: 1,138, Type 2: 314) and no rifaximin (N = 560; Type 3:337, Type 4: 223) treatment cohorts. The 30-day risk of OHE rehospitalization was lower for the rifaximin vs. no rifaximin treatment cohort (odds ratio 0.56, p < .01) and increased with decreasing QoC. The annual rate of OHE hospitalizations was 59% lower for the rifaximin treatment cohort (incidence rate ratio 0.41, p < .01) and increased with decreasing QoC. Compared to the no rifaximin treatment cohort, the rifaximin treatment cohort had higher pharmacy costs, lower medical costs, and no difference in total healthcare costs.LimitationsThis was a claims-based study subject to common data limitations such as billing inaccuracies or omissions in coded claims. Total healthcare costs were reported from a payer’s perspective, which do not capture indirect costs associated with patient burden.ConclusionsInitiation of rifaximin after an OHE hospitalization was associated with reduced OHE hospitalizations both in the 30-days following and annually. Further, reduced medical costs offset increased pharmacy costs, and no annual cost differences were observed between cohorts.

High rifaximin out-of-pocket costs are associated with decreased treatment retention among patients with hepatic encephalopathy.

Hepatic encephalopathy (HE) is associated with significant morbidity and mortality for those with cirrhosis. Despite the known benefits of rifaximin use for HE, treatment retention remains low. This study aimed to evaluate the impact of out-of-pocket (OOP) rifaximin cost on treatment retention among commercially insured patients in the United States. Adult patients with cirrhosis and HE were identified from the IBM MarketScan claims database. Those who began rifaximin treatment between January 1, 2011, and December 1, 2021 were included. Regression models were used to analyze the relationship between patients' 30-day OOP rifaximin cost and rifaximin retention (≥80% eligible days with rifaximin supply) at 180, 360, and 540 days. Models were controlled for patient demographic and clinical characteristics including age, sex, comorbid conditions, Charlson comorbidity index (CCI), and lactulose use. A total of 6839 adult patients were included. Most patients were between 55 and 64 years (57.1%), male (60.4%), and living in urban settings (84.6%). Treatment retention was low for all time periods; retention rates for rifaximin were 42%, 25%, and 16% at 180, 360, and 540 days, respectively. In multivariable analysis, 30-day OOP costs of ≥ $150 were associated with a decreased likelihood of rifaximin retention at 180, 360, and 540 days [relative risk (RR) = 0.67, RR = 0.62, and R = 0.60, respectively]. Younger age was associated with reduced treatment retention for all time periods. Metastatic cancer and depression were associated with reduced treatment retention at 180 days (RR = 0.70 and RR = 0.87, respectively). Rates of rifaximin treatment retention are low despite the known benefits of rifaximin use for breakthrough HE. High 30-day OOP cost is associated with reduced rifaximin treatment retention.

Rifaximin Use, Adherence and Persistence in Patients with Hepatic Encephalopathy: A Real-World Study in the South of Italy.

Real-world data on the therapeutic management of hepatic encephalopathy (HE) patients are limited. The aim of this study was to evaluate the HE medications prescribed in an Italian cohort of HE patients post-discharge and to assess the real-world rifaximin adherence and persistence over 1 year. An observation retrospective study was conducted using data retrieved from outpatient pharmaceutical databases and hospital discharge records of the Campania region. For all subjects hospitalized for HE during 2019 (cohort 1), the HE medications prescribed within 60 days after discharge were evaluated. Adherence (proportion of days covered, PDC) and persistence were estimated for rifaximin 550 mg incident users over 1 year (cohort 2). Patients with PDC ≥80% were considered adherents. Persistence was defined as the period of time from the first rifaximin prescription to the date of discontinuation. Discontinuation was assessed using the permissible gap method. In cohort 1, 544 patients were identified; 58.5% received rifaximin while 15.6% only received non-absorbable disaccharides and 25.9% did not receive any HE medications. In cohort 2, 650 users were selected; only 54.5% were adherents and 35% were persistent users at 1 year. This real-world study highlights that quality improvement in therapeutic management is needed to potentially improve the outcomes of HE patients.

SAT-339 - Impact of rifaximin use post-discharge of an overt hepatic encephalopathy (OHE) hospitalization on the annual rates of OHE-related inpatient stays

SAT-339 - Impact of rifaximin use post-discharge of an overt hepatic encephalopathy (OHE) hospitalization on the annual rates of OHE-related inpatient stays

Efficacy of Rifaximin in Diarrhoea Predominant Irritable Bowel Syndrome: A Placebo Controlled Clinical Trial

Introduction: Irritable bowel syndrome is a common chronic functional gastrointestinal disorder characterized by abdominal pain associated with altered bowel habit of either diarrhoea, constipation or both. Its pathogenesis is multifactorial and incompletely understood.The role of gut microbiota in the pathophysiology of IBS is supported by various evidences.These are 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 such as Rifaximin. Previous study showed resetting microbial diversity via Rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS. This study is designed to assess efficacy of Rifaximin in diarrhoea predominant irritable bowel syndrome. Objective: This study was conducted to assess the effectiveness of Rifaximin in diarrhoea predominant irritable bowel syndrome patient. Materials and Methods: This quasi experimental study was conducted on patients aged 18-55 years with IBS-D in department of Gastroenterology, BSMMU during the period of September, 2020 to August, 2021. Results: There was significant improvement on abdominal pain(p &lt;0.001), abdominal bloating(p =0.001) and satisfaction with bowel movement( p&lt;0.001) in Rifaximin group at 4th week from baseline and most of which sustained upto 12th week of study. The total IBS-SSS at baseline (328.7 ±13.7) decreased to (231.5±14.2) at 12th week of study in Rifaximin group which was significant (p &lt;o.oo1). In placebo group IBS-SSS also gradually decreased from baseline (323.4±17.29) to 12th week (269.3±16.2) but statistically not significant. IBS-QOL score at baseline in Rifaximin group was 64±5.2 and in placebo group was 63.4±5.1. Total IBS-QOL score was increased with time in both Rifaximin and placebo group but none was significant. Conclusion: Rifaximin was more effective than placebo in controlling abdominal pain, abdominal bloating and dissatisfaction with bowel movement after 12th week of study. IBS QOL score was also increased in both groups. Medicine Today 2023 Vol.35(1): 44-48

Gut metagenome-derived signature predicts hepatic decompensation and mortality in NAFLD-related cirrhosis.

There are limited data on the diagnostic accuracy of gut microbial signatures for predicting hepatic decompensation in patients with cirrhosis. To determine whether a stool metagenome-derived signature accurately detects hepatic decompensation and mortality risk in cirrhosis secondary to non-alcoholic fatty liver disease (NAFLD) METHODS: Shotgun metagenomic sequencing was performed on faecal samples collected at study entry from a prospective cohort of adults with NAFLD-related cirrhosis. A Random Forest machine learning algorithm was utilised to identify a metagenomic signature of decompensated cirrhosis (defined by ascites, hepatic encephalopathy or variceal haemorrhage) and subsequently validated in an external cohort. A Cox proportional hazards regression model was used to examine predictors of all-cause mortality. In all, 25 adults with NAFLD-related cirrhosis (training cohort) were included. Among the 16 participants with decompensated cirrhosis, 33% had ascites, 56% had hepatic encephalopathy and 22% had experienced a variceal haemorrhage (not mutually exclusive). We identified a stool metagenomic signature comprising 13 discriminatory species that reliably distinguished decompensated NAFLD-related cirrhosis (diagnostic accuracy, 0.97, 95% confidence interval [CI] 0.96-0.99). Diagnostic accuracy of the 13-species signature remained high after adjustment for lactulose (area under the curve [AUC] 0.99) and rifaximin use (AUC 0.93). The discriminative ability of 13-species metagenomic signature was robust in an independent test cohort (AUC 0.95, 95% CI 0.81-1.00). The 13-species metagenomic signature (hazard ratio [HR] 1.54, 95% CI 1.10-2.15, p= 0.01) was a stronger predictor of mortality than the Model for End-Stage Liver Disease score (HR 1.25, 95% CI 1.03-1.53, p= 0.03). This study provides evidence for a gut metagenome-derived signature with high diagnostic accuracy for hepatic decompensation that predicts risk of mortality in NAFLD-related cirrhosis.

Nonselective beta-blocker use is associated with increased hepatic encephalopathy-related readmissions in cirrhosis.

BACKGROUNDHepatic encephalopathy (HE) is a neurocognitive condition in cirrhosis leading to frequent hospitalizations. Nonselective beta-blockers (NSBBs) are the mainstay of pharmacologic treatment in cirrhotic patients. We hypothesized that since NSBBs decrease cardiac output and portal flow, the decreased metabolic filtering process of liver parenchyma may lead to increased HE-related hospitalizations.AIMTo evaluate the impact of NSBB administration on HE-related readmissions in cirrhotic patients.METHODSIn this retrospective cohort study, we included 393 patients admitted to Baylor University Medical Center for liver-related portal hypertension indications between January 2013 and July 2018. Independent predictors of the first HE-related readmissions were identified using Cox proportional hazards analysis. The cumulative incidence of the first HE-related readmissions between patients receiving NSBBs and not receiving NSBBs was examined using Fine-Gray modeling to account for the competing risk of death or liver transplantation.RESULTSThe mean age was 58.1 ± 10.2 years and most patients fell into Child class C (49.1%) or B (43.8%). The median Model for End-Stage Liver Disease-Sodium score was 22 (IQR: 11). The cumulative incidence of the first HE-related readmissions was significantly higher in patients taking NSBBs compared to patients not receiving NSBBs (71.8% vs 41.8%, P < 0.0001). In multivariate analysis, after adjusting for demographics, markers of liver disease severity, selective beta-blocker, lactulose and rifaximin use, NSBB use [Hazard ratio: 1.74 (95%CI: 1.29-2.34)] was independently associated with the first HE-related readmissions over a median follow-up of 3.8 years. CONCLUSIONNSBB use is independently associated with increased HE-related readmissions in patients with cirrhosis, regardless of liver disease severity.

Stool microbiota show greater linkages with plasma metabolites compared to salivary microbiota in a multinational cirrhosis cohort.

Cirrhosis is associated with changes in gut microbiota in both saliva and stool. The relative linkage patterns of stool versus saliva microbiota with systemic metabolomics are unclear and may differ across countries. We hypothesized that stool microbiota have greater linkages with plasma metabolites than saliva microbiota, which may depend on country of origin. Age-balanced controls and outpatient patients with cirrhosis, compensated and decompensated, from the USA and Mexico (MX) underwent plasma collection and dietary recall. Plasma metabolomics were analysed using nuclear magnetic resonance spectroscopy. Microbiota in stool and saliva samples were analysed using 16S rRNA analyses. Correlation network differences between both saliva and stool gut microbiota and plasma metabolites were compared between subject groupings and within/between countries. A total of 313 age-balanced subjects-135 USA (47 control, 48 compensated and 40 decompensated) and 178 MX (71 control, 56 compensated and 51 decompensated)-were enrolled. Cirrhosis severity, including lactulose and rifaximin use, were comparable. Plasma metabolites differed with advancing cirrhosis, between countries and according to 90-day hospitalizations. Correlation networks demonstrated more microbiome-metabolite linkages in stool compared to saliva in both populations, although there were no salivary correlation metrics across decompensated subjects in either country. Stool Lactobacillus showed a positive correlation to plasma lactate in decompensated cirrhosis from MX but not USA. Stool microbiota were more extensively linked with systemic metabolites than were saliva microbiota, irrespective of cirrhosis severity and country. These changes were more prominent in decompensated cirrhosis and were centred around plasma lactate, which might reflect the interaction of diet and lactulose therapy.

Lack of Access to Rifaximin Upon Hospital Discharge Is Frequent and Results in Increased Hospitalizations for Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a complication of cirrhosis. Rifaximin, added to lactulose, effectively maintains remission and reduces hospitalizations from HE compared with lactulose alone. Although the clinical evidence supports the use of rifaximin, concerns remain regarding the financial implications and subsequent impact on medication access and outcomes. The goal of this study was to determine whether medication access to rifaximin at hospital discharge reduces readmission and office visits related to HE. A retrospective study was conducted in compliance with local institutional review board including cirrhotic patients discharged with a rifaximin prescription for HE. Patients were stratified into 2 groups: those able to obtain rifaximin and those unable to obtain rifaximin upon discharge. The primary outcome was to evaluate the rate of HE recurrence in each group as defined as a composite of readmission or office visit for acute HE within 12 months of discharge. Access to rifaximin significantly reduced the risk of hospital admission and office visit for acute HE over 12 months. A hospitalization or office visit occurred in 24.5% of patients in the medication access group compared with 50% in the group without medication access. Only 58% of patients had access to rifaximin at discharge. Rifaximin use was associated with significantly reduced risk of hospitalization and office visits for HE. At discharge, 42% of patients did not have access to rifaximin regardless of being prescribed the medication, identifying that copay is a significant barrier in allowing patients to have access to rifaximin.

Racial and ethnic disparities in rifaximin use and subspecialty referrals for patients with hepatic encephalopathy in the United States

Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We sought to determine whether race and ethnicity were associated with rifaximin prescriptions. We examined data for a 20% random sample of United States Medicare enrollees with cirrhosis and hepatic encephalopathy treated with outpatient lactulose and Part D prescription coverage from 2011-2019. Beginning at the time of first diagnosis, we evaluated time to first prescription of rifaximin accounting for competing risks (Fine-Gray, yielding subdistribution hazard ratios [sHRs]) and cumulative rifaximin exposure using a gamma hurdle model (yielding exposure length ratios). We aimed to determine the association of race and ethnicity with each outcome, adjusting for demographics, clinical factors, and other features of clinical management. Overall, 29,095 patients were diagnosed with HE and treated with lactulose, of whom 13,272 were prescribed rifaximin. Compared to White patients, Black patients were least likely to receive any prescription for rifaximin (sHR 0.70; 95% CI 0.65-0.76). Asian and Hispanic patients were also less likely to receive rifaximin compared to White patients. Black patients also received fewer doses of rifaximin (exposure length ratio 0.90; 95% CI 0.82-0.98). Hispanic patients also received fewer doses (0.88; 95% CI 0.80-0.98). Out-of-pocket spending on rifaximin per person-year was higher for Black and Hispanic than White patients. Out-of-pocket medication spending was associated with reduced odds of filling a rifaximin prescription. Black and Hispanic patients were least likely to be referred to a gastroenterologist. In a national cohort of patients with HE, we observed stark racial and ethnic disparities in the use of rifaximin, an approved therapy for the improvement of HE-specific outcomes. Access to gastroenterologists and cost controls may reduce disparities. Hepatic encephalopathy is a serious problem that can affect people with cirrhosis. When someone develops hepatic encephalopathy, there are 2 main treatments. The first-line treatment is called lactulose. If episodes of hepatic encephalopathy happen on lactulose, another treatment called rifaximin is recommended. In this study, we found that compared to White patients, Black and Hispanic patients are less likely to be prescribed rifaximin, receive fewer rifaximin refills, spend more on rifaximin, and have less access to subspecialists who are familiar with rifaximin. We conclude that efforts to address the cost of rifaximin and access to gastroenterologists could help improve these disparities.

An Electronic Decision Support Intervention Reduces Readmissions for Patients With Cirrhosis.

Rifaximin use in combination with lactulose is associated with a decreased risk of overt hepatic encephalopathy (HE). We prospectively evaluated the impact of an interruptive electronic medical record alert to indicate rifaximin for patients with cirrhosis and HE on lactulose. The intervention was associated increased rifaximin utilization, particularly for nongastroenterology and hospitalist services odds ratio 1.20 95% confidence interval (1.09-1.31). For patients with HE, the intervention was associated with a lower readmission risk-adjusted subdistribution hazard ratio 0.63 95% confidence interval (0.48-0.82). An interruptive alert in the electronic ordering system was associated with a lower risk of readmissions.

Prevalence and outcomes of Clostridioides difficile infection in liver transplant recipients.

Data are limited on whether Clostridioides difficile infection (CDI) in the first year after liver transplantation (LT) is associated with increased mortality. In an Australian setting without hypervirulent strain of C. difficile we investigated the prevalence, risk factors, and patient survival associated with CDI in LT. Consecutive patients who underwent deceased-donor LT from 2007 to 2017 were studied retrospectively. Prevalence and long-term outcomes of LT recipients with and without CDI were examined in the entire LT cohort. A case-control study was performed to investigate risk factors associated with CDI. Six hundred and forty-nine patients underwent LT, of which 32 (4.9%) were diagnosed with CDI within the first 12 months post-LT. There was no difference in patient survival in the overall LT cohort on Kaplan-Meier analysis when stratified by CDI status (log-rank test, p=.08). Furthermore, age was the only predictor of mortality on Cox regression (hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.00-1.13, p=.03). On multivariable logistic regression, rifaximin pre-LT reduced risk (odds ratio (OR) 0.22, 95% CI 0.65-0.74, p=.01) whereas antibiotics pre-LT (OR 7.02, 95% CI 1.26-39.01, p=.03) and length of hospital stay after LT (OR 1.03, 95% CI 1.01-1.06, p=.02) were associated with increased risk of CDI. Within the local setting of our study, CDI within 12 months post-LT is of low severity, associated with pre-LT antibiotic exposure and longer hospital stay but no survival impact after LT. Rifaximin use pre-LT reduced the risk of CDI post-LT.

Stool microbiota are superior to saliva in distinguishing cirrhosis and hepatic encephalopathy using machine learning

Saliva and stool microbiota are altered in cirrhosis. Since stool is logistically difficult to collect compared to saliva, it is important to determine their relative diagnostic and prognostic capabilities. We aimed to determine the ability of stool vs. saliva microbiota to differentiate between groups based on disease severity using machine learning (ML). Controls and outpatients with cirrhosis underwent saliva and stool microbiome analysis. Controls vs. cirrhosis and within cirrhosis (based on hepatic encephalopathy [HE], proton pump inhibitor [PPI] and rifaximin use) were classified using 4 ML techniques (random forest [RF], support vector machine, logistic regression, and gradient boosting) with AUC comparisons for stool, saliva or both sample types. Individual microbial contributions were computed using feature importance of RF and Shapley additive explanations. Finally, thresholds for including microbiota were varied between 2.5% and 10%, and core microbiome (DESeq2) analysis was performed. Two hundred and sixty-nine participants, including 87 controls and 182 patients with cirrhosis, of whom 57 had HE, 78 were on PPIs and 29 on rifaximin were included. Regardless of the ML model, stool microbiota had a significantly higher AUC in differentiating groups vs. saliva. Regarding individual microbiota: autochthonous taxa drove the difference between controls vs. patients with cirrhosis, oral-origin microbiota the difference between PPI users/non-users, and pathobionts and autochthonous taxa the difference between rifaximin users/non-users and patients with/without HE. These were consistent with the core microbiome analysis results. On ML analysis, stool microbiota composition is significantly more informative in differentiating between controls and patients with cirrhosis, and those with varying cirrhosis severity, compared to saliva. Despite logistic challenges, stool should be preferred over saliva for microbiome analysis. Since it is harder to collect stool than saliva, we wanted to test whether microbes from saliva were better than stool in differentiating between healthy people and those with cirrhosis and, among those with cirrhosis, those with more severe disease. Using machine learning, we found that microbes in stool were more accurate than saliva alone or in combination, therefore, stool should be preferred for analysis and collection wherever possible.

Review of Rifaximin: A Summary of the Current Evidence and Benefits Beyond Licensed Use

Antibiotic resistance in patients with cirrhosis continues to draw significant attention. With a propensity to frequent hospitalisations, patients with cirrhosis are subject to frequent antibiotic prescription. This increases their risk of developing resistance to one or more antimicrobial agents, making management of their condition particularly challenging. Despite advancements being made in the management of liver disease, mortality rates continue to rise: almost 5-fold in those &lt;65 years of age while remaining the leading cause of death in those 35–49 years of age. Alternative therapeutic options to prevent disease progression and cirrhosis-associated complications are urgently required; rifaximin is one such example. The medication use in patients with cirrhosis demonstrates additional benefits beyond current licensed use in the UK, that being for the prevention of hepatic encephalopathy and traveller’s diarrhoea; rifaximin has especially been explored beyond current licensed use in the context of enteric-driven pathologies. Through the therapy’s key central action as a broad-spectrum antimicrobial, rifaximin has the ability to modulate the gut–liver axis via removal of gut microbial products associated with the progression of cirrhosis and its sequalae. The benefits of rifaximin use continues to gather momentum, given its non-absorbable nature and well-tolerated side-effect profile, and these require consideration. With broad-spectrum antimicrobial properties, its use may assist in overcoming the conundrum posed of antibiotic resistance amongst patients with cirrhosis. This literature review discusses the chemical and antimicrobial properties of rifaximin, its licenced indication for use, and its reported benefits beyond this, as well as concerns regarding rifaximin resistance.

Predictors of hepatorenal syndrome in patient with decompensated liver cirrhosis

Introduction: Hepatorenal syndrome (HRS) is one of the severe complications of decompensated liver cirrhosis which has poor outcome. Predictive models are important aspect in assessment of high risk patient.&#x0D; Method: This prospective analytical study was conducted in Gastroenterology unit of Bir hospital from December 2018 to April 2020. Seventy patient of liver cirrhosis with ascites (CTP score 7 or more) were followed for a period of three months. The outcome of study was hepatorenal syndrome. Predictors were assessed from baseline variables.&#x0D; Result: Total 65 patients completed the study. The mean age of study population was 47.38 ±11.38 years and 52(80%) were male. The most common aetiology was alcohol 55(84 %). Eight (12.5%) developed HRS. Hepatorenal syndrome was precipitated by spontaneous bacterial peritonitis 5(62.5%), upper gastrointestinal bleeding 2(25%) and unknown 1(12.5%). In Bivariate analysis total leucocyte count, Serum sodium, Model for End-stage Liver Disease – Sodium (MELD- Na), serum bilirubin and use of rifaximin were predictors of HRS. Only use of rifaximin was the predictor in multivariate analysis.&#x0D; Conclusion: Serum sodium, bilirubin and MELD Na are important predictors of the hepatorenal syndrome. Rifaximin use may be preventive for HRS.&#x0D; Keywords: Decompensation, hepatorenal syndrome, liver cirrhosis, predictors