Efficacy and safety of rifaximin in the prevention of spontaneous bacterial peritonitis: A Meta-analysis / 临床肝胆病杂志

ObjectiveTo evaluate the efficacy and safety of rifaximin in the prevention of spontaneous bacterial peritonitis (SBP). MethodsCNKI, Wanfang Data, CBM, PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) and cohort studies on rifaximin in the prevention of SBP published up to July 5, 2020. The articles were screened according to the inclusion and exclusion criteria, and data extraction and quality assessment were performed. RevMan 5.3 software was used to conduct the meta-analysis. Results A total of 13 studies (with 2207 patients in total) were included, among which there were 6 RCTs and 7 cohort studies. The results of the meta-analysis showed that compared with the non-prevention group, the rifaximin group had significantly lower incidence rate of SBP (odds ratio ［OR］=0.36, 95% confidence interval ［CI］: 0.14-0.96, P=0.04) and mortality rate (OR=0.59, 95% CI: 037-0.95, P=0.03); compared with the norfloxacin group, the rifaximin group had significantly lower incidence rate of SBP (OR=039, 95% CI: 025-0.62, P＜0.001), mortality rate (OR=0.55, 95% CI: 0.34-0.92, P=0.02), and adverse reactions (OR=0.36, 95% CI: 0.22-059, P＜0.001). The subgroup analysis based on the type of prevention showed that there was no significant difference in primary prevention between the two groups (OR=0.56, 95% CI: 0.23-1.35, P=0.20), and in secondary prevention, the rifaximin group had a significantly lower incidence rate of SBP (OR=0.18, 95% CI: 0.08-0.43, P＜0.001). In addition, it was also found that rifaximin significantly reduced the incidence rate of hepatorenal syndrome (OR=0.34, 95% CI: 0.15-0.77, P=0.01) and hepatic encephalopathy (OR=0.55, 95% CI: 0.32-0.95, P=0.03). ConclusionRifaximin is safe and effective for the primary and secondary prevention of SBP. Rifaximin is superior to norfloxacin in secondary prevention, which still needs to be confirmed by high-quality multicenter RCTs.

Reference Value of Fecal Bacterial Smear for Antibiotic Treatment in Irritable Bowel Syndrome With Diarrhea / 胃肠病学

Background: Intestinal microbiota dysbiosis is closely related to irritable bowel syndrome (IBS). Fecal bacterial smear is a simple and economical laboratory test for determining the severity of this condition. Aims: To explore the reference value of fecal bacterial smear for antibiotic treatment in IBS with diarrhea (IBS-D). Methods: A total of 130 IBS-D patients were enrolled and allocated into four groups according to the results of fecal bacterial smear: normal intestinal microbiota group and grade , Ⅱ and III dysbiosis groups. Patients with grade III dysbiosis were treated based on fecal bacterial culture and drug susceptible test; patients in other three groups were treated with rifaximin for 7 days. After 7-day rifaximin treatment, all patients were reviewed for fecal bacterial smear. The clinical efficacy and changes in fecal bacterial smear were assessed and the consistency of these two aspects was analyzed by Kappa coefficient. Results: Of the 130 IBS-D patients, 82.3% had intestinal microbiota dysbiosis, and those with grade , Ⅱ and III dysbiosis was 48.5%, 25.4%, and 8.5%, respectively. The overall efficacy of rifaximin in patients with grade +Ⅱ dysbiosis was significantly higher than that in patients with normal intestinal microbiota (57.3% vs. 30.4%, P<0.05). Furthermore, the overall efficacies in grade and grade Ⅱ dysbiosis groups, especially in grade Ⅱ dysbiosis group, were consistent with the changes in fecal bacterial smear (κ=0.653 and κⅡ=0.727, all P<0.05). Conclusions: Intestinal microbiota dysbiosis can be detected in a great proportion of patients with IBS-D, and antibiotic treatment is more effective in patients with dysbiosis. Fecal bacterial smear might be used to stratify the IBS-D patients for optimal selection of antibiotics.

Diferencias farmacocinéticas entre rifaximina alfa y una rifaximina genérica / Pharmacokinetic differences between alpha rifaximin and a generic rifaximin

Resumen: ANTECEDENTES: Los fármacos que tienen polimorfismo, como la rifaximina, pueden tener diferencias farmacocinéticas según el polimorfo. La rifaximina polimorfa-α (alfa) es un antibiótico no absorbible. OBJETIVO: Investigar si la farmacocinética de la rifaximina de referencia (α) es distinta de la de una rifaximina genérica en el mercado mexicano. MATERIAL Y MÉTODO: Estudio prospectivo experimental del polimorfo con difracción de rayos X, su perfil de solubilidad y la farmacocinética de una dosis única de 100 mg/ kg de cada rifaximina administrada por vía oral en perros Beagle. RESULTADOS: La rifaximina de referencia fue polimorfo-α (alfa) y la rifaximina genérica resultó polimorfo-к (kappa). El perfil de solubilidad fue diferente porque el polimorfo-к fue más soluble que el α. La concentración plasmática máxima (Cmáx), la concentración durante 24 horas (AUC0-t) y la biodisponibilidad relativa fueron 8 a 10 veces mayores con rifaximina genérica (к) que con la de referencia (α). CONCLUSIÓN: La rifaximina genérica estudiada tiene farmacocinética distinta del producto de referencia y no puede considerarse del todo un antibiótico no absorbible. Se discuten las posibles implicaciones terapéuticas, especialmente en la seguridad.

Abstract: BACKGROUND: Drugs with polimorphism, as rifaximin, may have different pharmacokinetic depending on the polymorph. Rifaximin polymorph-α (alfa) is a non-absorbable antibiotic. OBJECTIVE: To investigate if pharmacokinetic of reference rifaximin (α) is different from a generic rifaximin of the Mexican market. MATERIAL AND METHOD: A prospective experimental study was done assessing polymorphism with X-ray diffraction, solubility test and pharmacokinetics in Beagle dogs after unique oral dose of 100 mg/kg of each rifaximin. RESULTS: Reference rifaximin was a polymorph-α (alfa), while generic rifaximin resulted a polymorph-к (kappa). Solubility profile of both was different, solubility of generic was major than reference rifaximin. Plasma peak concentration (Cmax), area under curve (AUC0-t) and relative bioavailability were 8 to 10 folds higher with generic rifaximin (к) than reference drug (α). CONCLUSION: Generic rifaximin has a different pharmacokinetic from the reference rifaximin and the former cannot be considered a non-absorbable antibiotic.

Preferential usage of rifaximin for the treatment of hydrogen-positive small intestinal bacterial overgrowth / Rifaximina como tratamiento de elección en pacientes con sobrecrecimiento bacteriano con prueba de hidrógeno positiva

Objectives: Small intestinal bacterial overgrowth (SIBO) is challenging to treat and diagnose and is associated with diagnosis of irritable bowel syndrome (IBS). Although no FDA-approved medications exist for treatment of SIBO, rifaximin has recently received approval to treat diarrhea-predominant IBS and patients with methane-positive SIBO breath tests. The aim of this study is to evaluate patient response to rifaximin for SIBO based on breath test results. Materials and methods: All patients underwent breath testing to evaluate for SIBO during a 42-month period. Patients were defined as having a positive glucose breath test for SIBO based on an increase of ≥ 20 ppm of hydrogen and/or ≥ 10 ppm of methane 90 minutes after ingesting glucose. Patient demographic and symptom data, antibiotic treatment regimens, symptomatic response to therapy, and repeat treatments were recorded. Institutional review board approval was obtained. Results: A total of 53 of 443 patients had positive breath testing for SIBO. Response rates to rifaximin (550 mg three times daily for 14 days) were 47.4% for hydrogen positivity alone and 80% for both hydrogen and methane positivity. Conclusions: Rifaximin was the most commonly prescribed antibiotic regimen for SIBO therapy. Patients with hydrogen or hydrogen and methane positive breath tests responded well to rifaximin therapy. For patients with hydrogen-positive SIBO, rifaximin may prove a highly effective therapy in providing symptom relief from the effects of SIBO.

Objetivos: El sobrecrecimiento bacteriano de intestino delgado es una entidad difícil de diagnosticar y tratar, frecuentemente asociada con el síndrome de intestino irritable. A pesar que la FDA no ha aprobado medicamentos para tratar el sobrecrecimiento bacteriano, la rifaximina ha sido recientemente aprobada para tratar el intestino irritable tipo diarrea y en pacientes con test de aliento metano positivo en sobrecrecimiento bacteriano. El objetivo del estudio fue evaluar la respuesta a rifaximina de los pacientes con sobrecremiento bacteriano con prueba de aliento positiva. Material y métodos: Todos los pacientes que se realizaron prueba de aliento por sobrecrecimiento bacteriano durante un periodo de 42 meses. Se definió un paciente con sobrecrecimiento bacteriano positivo si tenía un incremento mayor a 20 ppm de hidrógeno y/o 10 ppm de metano luego de 90 minutos de la ingesta de glucosa. Se registraron los datos demográficos, síntomas, tratamiento antibióticos recibidos, respuesta a la terapia, y repetición de tratamientos. Resultados: Un total de 53 de 443 pacientes tuvieron prueba de aliento positiva para sobrecrecimiento bacteriano. La tasa de respuesta a rifaximina (550 mg tres veces x día x 14 días) fue 47.4% para pacientes con sólo test de hidrógeno positivo, y 80% para pacientes con tanto test de hidrógeno como metano positivos. Conclusiones: La rifaximina es el régimen antibiótico más frecuentemente utilizado en sobrecrecimiento bacteriano. Los pacientes con prueba de aliento de hidrógeno o hidrógeno y metano positivos respondieron bien a la rifaximina. Para pacientes con sobrecrecimiento bacteriano prueba de hidrógeno positiva, la rifaximina puede ser una terapia efectiva en mejorar síntomas.

Efficacy of low dose and short-term rifaximin on irritable bowel syndrome related with small intestinal bacterial overgrowth / 中华消化杂志

Objective To investigate the efficacy of low dose and short-term oral rifaximin in patients with small intestinal bacterial overgrowth (SIBO)related irritable bowel syndrome (IBS). Methods From June 2017 to June 2018,at the Department of Gastroenterology of Huashan Hospital,Fudan University in Shanghai,a total of 37 patients with SIBO related IBS were sequentially enrolled and divided into three groups:diarrhea type,constipation type and mixed type. All the patients received rifaximin 200 mg each time,three times per day for 14 days. The clinical efficacy before and after treatment were compared by the scores of irritable bowel syndrome symptom severity scale (IBS-SSS)and irritable bowel syndrome associated quality of life (IBS-QoL). The efficacy of rifaximin on SIBO clearance and SIBO related chronic low-grade inflammation was evaluated by lactulose breath test (LBT)and exhaled nitric oxide (eNO). T test and variance analysis were used for statistical analysis. Results Among 39 patients with SIBO related IBS,24 patients were diarrhea type,seven were constipation type and six were mixed type. Except one patient quitted the study because of chest tightness and palpitation,the IBS-SSS score of the left 36 patients before treatment was (250. 83 ± 55. 10),and decreased to (151. 11 ± 33. 96),and the difference was statistically significant (t = 13. 686,P <0. 01). Before treatment the score of IBS-QoL was (28. 03 ± 16. 16),and decreased to (14. 39 ± 9. 31)after treatment,and the difference was statistically significant (t = 6. 867,P < 0. 01 ). There was no significant difference in IBS-SSS and IBS-QoL scores among the diarrhea type,constipation type and mixed type groups (all P > 0. 05). After treated by rifaximin,the negative conversion rate of SIBO was 52. 8％(19 / 36). The negative conversion rate of hydrogen LBT was 54. 5％(12 / 22)and among 11 methane LBT positive patients,six cases turned negative;and one of three patients with both positive hydrogen LBT and methane LBT turned negative. The negative conversion rate of eNO was 41. 7％ (15 / 36). Conclusions Low dose and short term rifaximin treatment can improve the severity of clinical symptoms and quality of life in SIBO-related IBS patients,and the efficacy is not related with the subtypes of IBS.

Efficacy of low dose and short-term rifaximin on irritable bowel syndrome related with small intestinal bacterial overgrowth / 中华消化杂志

Objective@#To investigate the efficacy of low dose and short-term oral rifaximin in patients with small intestinal bacterial overgrowth (SIBO) related irritable bowel syndrome (IBS).@*Methods@#From June 2017 to June 2018, at the Department of Gastroenterology of Huashan Hospital, Fudan University in Shanghai, a total of 37 patients with SIBO related IBS were sequentially enrolled and divided into three groups: diarrhea type, constipation type and mixed type. All the patients received rifaximin 200 mg each time, three times per day for 14 days. The clinical efficacy before and after treatment were compared by the scores of irritable bowel syndrome symptom severity scale (IBS-SSS) and irritable bowel syndrome associated quality of life (IBS-QoL). The efficacy of rifaximin on SIBO clearance and SIBO related chronic low-grade inflammation was evaluated by lactulose breath test (LBT) and exhaled nitric oxide (eNO). T test and variance analysis were used for statistical analysis.@*Results@#Among 39 patients with SIBO related IBS, 24 patients were diarrhea type, seven were constipation type and six were mixed type. Except one patient quitted the study because of chest tightness and palpitation, the IBS-SSS score of the left 36 patients before treatment was (250.83±55.10), and decreased to (151.11±33.96), and the difference was statistically significant (t=13.686, P<0.01). Before treatment the score of IBS-QoL was (28.03±16.16), and decreased to (14.39±9.31) after treatment, and the difference was statistically significant (t=6.867, P<0.01). There was no significant difference in IBS-SSS and IBS-QoL scores among the diarrhea type, constipation type and mixed type groups (all P>0.05). After treated by rifaximin, the negative conversion rate of SIBO was 52.8%(19/36). The negative conversion rate of hydrogen LBT was 54.5%(12/22) and among 11 methane LBT positive patients, six cases turned negative; and one of three patients with both positive hydrogen LBT and methane LBT turned negative. The negative conversion rate of eNO was 41.7%(15/36).@*Conclusions@#Low dose and short term rifaximin treatment can improve the severity of clinical symptoms and quality of life in SIBO-related IBS patients, and the efficacy is not related with the subtypes of IBS.

Effect of Rifaximin on Visceral Sensitivity via TRPV1-VGLUT2/3 Pathway in Rats / 胃肠病学

Background: Rifaximin has obvious effect on relieving abdominal pain in patients with irritable bowel syndrome, but the mechanism is not clear. Aims: To investigate the effect and mechanism of rifaximin on visceral sensitivity in rats. Methods: Chronic water avoidance stress (WAS) model was established in rats, and rats were divided into control group, WAS group and rifaximin group. Electromyogram was used to evaluate the visceral sensitivity. Immunological activities of TRPV1 and VGLUT2/3 in L6S1 DRG were determined by immunofluorescence, protein expressions of TRPV1 and VGLUT2/3 in L6S1 spinal cord were determined by Western blotting. Bacterial 16S rDNA sequencing analysis for intestinal flora was performed. Results: WAS could induce visceral hyperalgesia in rats, immunological activities of TRPV1 and VGLUT2/3 in L6S1 DRG were significantly increased, protein expressions of TRPV1 and VGLUT2/3 in L6S1 spinal cord were significantly increased, and imbalance of intestinal flora was induced. Rifaximin could ameliorate visceral hyperalgesia; immunological activities of TRPV1 and VGLUT2/3 in L6S1 DRG and protein expressions of TRPV1 and VGLUT2/3 in L6S1 spinal cord were significantly decreased; imbalance of intestinal flora was ameliorated. TRPV1 antagonist could significantly decrease the immunological activities of VGLUT2/3. Conclusions: Rifaximin can ameliorate the visceral hyperalgesia induced by WAS via intestinal flora and TRPV1-VGLUT2/3 pathway.

El impacto del tratamiento de la encefalopatía hepática mínima en el pronóstico a largo plazo / The impact of minimal hepatic encephalopathy treatment in long-term prognosis

La encefalopatía hepática mínima (EHm) afecta del 30% al 50% de los pacientes cirróticos. Su detección es esencial por su relación con la encefalopatía hepática clínica, la alteración de la habilidad para conducir, el mayor riesgo de caídas, la alteración de la calidad de vida, la progresión más acelerada de la cirrosis y la supervivencia. A pesar de la información fidedigna de su relevancia clínica, pronóstica y social, la detección de EHm no está generalizada en la práctica clínica. El espectro de la encefalopatía hepática engloba diversas alteraciones de las funciones cerebrales, por lo que se requiere realizar más de un test para su diagnóstico. Además, las alteraciones iniciales difieren de un paciente a otro. Esto ha dificultado el desarrollo de una estrategia diagnóstica universal. Como resultado, no disponemos de datos suficientes para generar recomendaciones basadas en la evidencia del impacto del tratamiento de la EHm en la calidad de vida y la supervivencia, así como de su rentabilidad. Por lo tanto, las guías clínicas actuales sugieren que se evalúe la EHm cuando se afecta la calidad de vida de los pacientes, ya que no se conocen las consecuencias del tamizaje. Las terapias reductoras de amonio se consideran la piedra angular del tratamiento de la EHm. Los disacáridos no absorbibles, la rifaximina y, más recientemente, los probióticos, han mostrado efectos beneficiosos. Se necesitan más ensayos controlados con placebo para evaluar la eficacia, seguridad y rentabilidad de los regímenes de tratamiento disponibles para evaluar el impacto del tratamiento de la EHm en el pronóstico a largo plazo de estos pacientes.

Minimal hepatic encephalopathy (MHE) affects up to 30-50% of cirrhotic patients. The detection of MHE is essential because of its relationship with overt hepatic encephalopathy, impairment of motor vehicle driving abilities, higher risk of falls, quality of life impairment, faster cirrhosis progression and survival. Despite the robust evidence regarding its clinical, prognostic and social relevance, MHE testing is not widespread in routine clinical care. Hepatic encephalopathy spectrum covers various alterations in complex brain functions, requiring more than one test to be quantified. In addition, initial disturbances differ from one patient to another. All this has made it difficult to develop a universal diagnostic strategy. As a consequence, there is a lack of available robust data in the literature to generate evidence-based recommendations related to the impact of MHE treatment on quality of life and survival of these patients, as well as on cost-effectiveness. Therefore, current clinical guidelines suggest MHE testing only when patients have problems with their quality of life, since consequences of the screening procedure are still unclear. Ammonia lowering therapies have been considered the cornerstone of MHE treatment. Beneficial effects of non-absorbable disaccharides (lactulose or lactitol), rifaximin and more recently, probiotics have been reported. Further placebo-controlled trials are needed to assess the efficacy, safety, and cost-effectiveness of available treatment regimes to evaluate the impact of MHE treatment on the long-term prognosis of these patients.

Clinical Response of Rifaximin Treatment in Patients with Abdominal Bloating / 대한소화기학회지

BACKGROUND/AIMS: Abdominal bloating is a troublesome complaint due to insufficient understanding of the pathophysiology. The aim of this study was to evaluate the efficacy of rifaximin in reducing bloating associated with functional gastrointestinal disorders (FGIDs). METHODS: A total of 63 patients were treated with rifaximin for FGIDs with bloating or gas-related symptoms between 2007 and 2013 at Seoul National University Bundang Hospital. Rifaximin was administered at a dose between 800 mg/day and 1,200 mg/day for 5 to 14 days. The proportion of patients who had adequate relief of global FGID symptoms and FGID-related bloating was retrospectively assessed. The response was recorded when the symptoms were reduced by at least 50% at the follow-up after treatment cessation. RESULTS: The mean age was 56.8±14.2 years; 49.2% were females. According to Rome III criteria, 20.6% (13/63) had irritable bowel syndrome (IBS) with constipation, 9.5% (6/63) had IBS with diarrhea, 4.8% (3/63) had mixed IBS, 23.8% (15/63) had functional dyspepsia, and 12.7% (8/63) had functional bloating. Of the 51 subjects who were followed-up, 30 (58.8%) had adequate relief of global FGID symptoms and 26 (51.0%) experienced improvement of abdominal bloating after rifaximin treatment. The proportion of female was slightly higher in non-response group than in the response group (60.0% vs. 34.6%, p=0.069). Otherwise, there was no difference between the two groups. CONCLUSIONS: Despite the limitations of this retrospective study, our data confirms that rifaximin may be beneficial for abdominal bloating. Further prospective clinical trial with a larger cohort is needed.

Minimal Hepatic Encephalopathy in Cirrhosis- How Long to Treat?

Abstract: Introduction. Minimal hepatic encephalopathy (MHE) can reverse after short-term treatment. However, relapse rate of MHE after stopping treatment has not been studied so far. We aimed to evaluate long-term (9 months) efficacy of a short-term (3 months) treatment of MHE with lactulose/rifaximin, for maintenance of remission from MHE. Material and methods. In this prospective study, consecutive patients with cirrhosis and MHE were treated with lactulose/rifaximin for 3 months. After treatment, they were followed up for 6 months. Psychometric testing for diagnosis of MHE was performed at baseline, 3 months and 9 months. Results. Of the 527 patients screened, 351 were found eligible and tested for MHE. Out of these, 112 (31.9%) patients had MHE (mean age 55.3 years; 75% males). They were randomized to receive Rifaximin (n = 57; 1,200 mg/day) or Lactulose (n = 55; 30-120 mL/day) for three months. At 3 months, 73.7% (42/57) patients in Rifaximin group experienced MHE reversal compared to 69.1% (38/55) in Lactulose group (p = 0.677). Six months after stopping treatment, 47.6% (20/42) in rifaximin group and 42.1% (16/38) patients in lactulose group experienced MHE relapse (p = 0.274). The overt hepatic encephalopathy development rate (7.1% vs. 7.9%) and mortality rate (0.23% vs. 0%) were similar in both groups. The Child-Turcotte-Pugh score and model for end stage liver disease (MELD) scores of patients who had MHE relapse were higher compared to those who didn’t. On multivariate regression analysis, MELD score was an independent predictor of MHE relapse. Conclusion. Of the patients who became MHE negative after short-term (3 months) treatment with rifaximin/lactulose, almost 50% had a relapse of MHE at 6 months follow-up.

Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study

BACKGROUND/AIMS: Non-selective beta blockers (NSBBs) are currently the only accepted regimen for preventing portal hypertension (PHT)-related complications. However, the effect of NSBBs is insufficient in many cases. Bacterial translocation (BT) is one of the aggravating factors of PHT in cirrhosis; therefore, selective intestinal decontamination by rifaximin is a possible therapeutic option for improving PHT. We investigated whether the addition of rifaximin to propranolol therapy can improve hepatic venous pressure gradient (HVPG) response. METHODS: Sixty-four cirrhosis patients were randomly assigned to propranolol monotherapy (n=48) versus rifaximin and propranolol combination therapy (n=16). Baseline and post-treatment HVPG values, BT-related markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]), serological data, and adverse event data were collected. HVPG response rate was the primary endpoint. RESULTS: Combination therapy was associated with better HVPG response rates than monotherapy (56.2% vs 87.5%, p=0.034). In combination therapy, posttreatment BT-related markers were significantly decreased (LPS, p=0.005; LBP, p=0.005; IL-6, p=0.005; TNF-α, p=0.047). CONCLUSIONS: Rifaximin combination therapy showed an additive effect in improving PHT compared to propranolol monotherapy. These pilot data suggest that the addition of rifaximin to NSBBs could be a good therapeutic option for overcoming the limited effectiveness of NSBBs.

Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy

The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this paradigm shift is the realization that gut dysbiosis, including small intestinal bacterial overgrowth (SIBO), causes IBS symptoms. Between 4% and 78% of patients with IBS and 1% and 40% of controls have SIBO; such wide variations in prevalence might result from population differences, IBS diagnostic criteria, and, most importantly, methods to diagnose SIBO. Although quantitative jejunal aspirate culture is considered the gold standard for the diagnosis of SIBO, noninvasive hydrogen breath tests have been popular. Although the glucose hydrogen breath test is highly specific, its sensitivity is low; in contrast, the early-peak criteria in the lactulose hydrogen breath test are highly nonspecific. Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients. Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut, providing support for the micro-organic basis of IBS. A recent proof-of-concept study showing the high frequency of symptom improvement in patients with IBS with SIBO further supports this hypothesis.

Effect of Rifaximin on Hepatic Fibrosis in Bile Duct-ligated Rat Model / 대한소화기학회지

BACKGROUND/AIMS: The translocation of bacteria and their lipopolysaccharides from the gut can promote fibrosis in cirrhotic patients. The aim of this study was to investigate the effects of rifaximin on hepatic fibrosis in a bile duct-ligated rat model. METHODS: The bile duct ligation (BDL) was carried out for eight days (acute injury model: sham-operated rats [G1], BDL rats [G2], and BDL rats treated with rifaximin [G3]) or 22 days (chronic injury model: sham-operated rats [G4], BDL rats [G5], and BDL rats treated with rifaximin [G6]). Rifaximin (50 mg/kg/day) was administered daily via gavage after BDL. Liver function, serum tumor necrosis factor-alpha (TNF-α), and hepatic hydroxyproline levels were measured. Moreover, a histological analysis of fibrosis contents was performed using sirius red stain. RESULTS: In the acute injury model, the liver function and TNF-α level were not improved after the rifaximin treatment. The hydroxyproline levels (µg/g liver tissue) in G1, G2, and G3 were 236.4±103.1, 444.8±114.4, and 312.5±131.6, respectively; and fibrosis contents (%) were 0.22±0.04, 1.64±0.53, and 1.66±0.44, respectively. The rifaximin treatment did not ameliorate acute BDL-induced fibrosis. In the chronic injury model, the hydroxyproline levels in G4, G5, and G6 were 311.5±72.9, 1,110.3±357.9, and 944.3±209.3, respectively; and fibrosis contents (%) were 0.19±0.03, 5.04±0.18, and 4.42±0.68, respectively (G5 vs. G6, p=0.059). The rifaximin treatment marginally ameliorated chronic BDL-induced fibrosis. CONCLUSIONS: Rifaximin did not reduce inflammation and fibrosis in bile duct-ligated rat model.

Problems and countermeasures in diagnosis and treatment of covert hepatic encephalopathy / 第二军医大学学报

Covert hepatic encephalopathy (CHE) is defined as presence of neuropsychological and/or neurophysiological abnormalities in cirrhotic patients without disorientation or asterixis. The West-Haven criteria are most often used to grade hepatic encephalopathy (HE), with scores ranging from 0 to 4. In 2011, the minimal (grade 0) and grade 1 hepatic encephalopathy were collectively referred to as CHE by SONIC classification. It is difficult for clinicians to diagnose CHE because its clinical manifestation is not obvious. So far, there is no consensus on CHE treatment. Here we have reviewed the articles regarding the diagnoses and treatment of CHE, hoping to provide guidance for the clinicians in clinical practice.

Actualización sobre enfrentamiento y manejo en encefalopatía hepática / Update on how to approach and manage hepatic encephalopathy

La encefalopatía hepática (EH) es una complicación grave y frecuente del daño hepático crónico (DHC), que se diagnostica clínicamente luego de descartar otras causas de disfunción cerebral. Su manejo consiste en identificar y corregir los factores desencadenantes, disminuir los niveles de amonio con disacáridos no reabsorbibles y eventualmente el uso de antibióticos de baja absorción intestinal, de preferencia rifaximina.

Hepatic encephalopathy is a serious and frequent complication of chronic liver disease and its clinical diagnosis is arrived at once other causes of cerebral dysfunction have been ruled out. It is managed by identifying and correcting triggering factors, lowering plasma ammonium levels by use of non-absorbable disaccharides and oral use of poorly absorbed antibiotics, preferably rifaximin.

Determination of Rifaximin Treatment Period According to Lactulose Breath Test Values in Nonconstipated Irritable Bowel Syndrome Subjects

Small intestinal bacterial overgrowth (SIBO) can partly explain irritable bowel syndrome (IBS), and rifaximin has been observed to improve abdominal symptoms in nonconstipated IBS patients. However, there are few reports on the association of the rifaximin treatment periods with the results of a lactulose breath test (LBT). Therefore, we performed a retrospective review of patient charts to investigate the relation between the rifaximin treatment periods with LBT results in nonconstipated IBS patients. We also evaluated the time to achieve a symptomatic improvement in the IBS patients as compared to the changes in the LBT. We reviewed the charts for patients who showed IBS symptoms with documented positive results for LBT during their initial visit and who had a follow-up LBT after treatment with rifaximin. The LBT values were compared to the subjects' symptom scores. A total of 102 subjects had a follow-up LBT to assess LBT normalization. The subjects were divided into groups according to treatment periods of 4 weeks (n = 36), 8 weeks (n = 43), and 12 weeks (n = 23). The groups with a longer treatment exhibited an increase in the hydrogen gas value at 90 min and its sum during 90 min at the initial LBT. There were significant differences in hydrogen gas value at 90 min and in its sum during 90 min at the initial LBT between the groups treated for 4 and 12 weeks. The most significant treatment response was observed during the first 4 weeks for all treatment groups. Symptomatic improvement occurred earlier than LBT normalization in the treatment period over 4 weeks. The results indicate that different rifaximin treatment periods are needed in accordance with LBT levels to effectively eradicate SIBO.

High Prevalence of Small Intestinal Bacterial Overgrowth in Lactose Intolerance Patients: Is It a Chicken and Egg Situation.

Background: Lactose intolerance is highly prevalent in Mediterranean area. Substantial portions of patients remain symptomatic in spite of fair lactose-free diet. Aims: Assess in a series of IBS consecutive patients: 1) the prevalence of lactose intolerance; 2) the frequency of association of lactose intolerance with SIBO; 3) the possibility of SIBO as a cause of symptom persistence in patients with lactose intolerance on lactose-free diet; 4) the ability of LHBT to diagnose SIBO. Place and Duration of the Study: Patients were recruited from November 2011 to July 2012 at the Gastroenterology Unit of Mauriziano Hospital U.Ist , Turin, Italy. Methodology: Lactose malabsorption was assessed by means of LHBT and SIBO by means of GHBT and LHBT, using Breath Tracker digital microlyzer on 500 IBS patients and 50 controls. SIBO was treated, with rifaximin 1200 mg a day for 2 weeks, randomly, on 1 to 1 basis. Results: Prevalence of lactose intolerance resulted to be 59% in IBS patients and 6% in controls, with a statistically significant difference (p<.001). SIBO was present in 72% of patients with lactose intolerance in IBS group, ad in none of the subjects with lactose malabsorption (3) in control group. After 6 months, 105 out of 106 patients affected by LI + SIBO treated with rifaximin + lactose free diet, and 34 out of 107 patients affected by LI + SIBO treated only with a lactose free diet resulted completely asymptomatic. Concordance between LHBT and GHBT for SIBO diagnosis was 98%. Conclusions: Lactose intolerance is a common condition in patients with IBS in Northwest Italy (59%) very frequently associated with SIBO (72%). This association turned out to be a major cause of symptom persistence in patients on lactose-free diet until successful eradication of SIBO was achieved. LHBT is a simple test able to diagnose simultaneously lactose malabsorption and SIBO.

Advances on clinical application of non-absorbable antibiotic rifaximin / 中华临床感染病杂志

Rifaximin as a representative of the non-absorbable antibiotics,has special effects and wide application prospects in treatments of acute intestinal tract infections,irritable bowel syndrome,inflammatory bowel disease,diverticulosis of colon,hepatic encephalopathy and so on.This paper reviews the advances on clinical efficacy and safety of rifaximin to provide reference for clinical use.

Abdominal Bloating: Pathophysiology and Treatment

Abdominal bloating is a very common and troublesome symptom of all ages, but it has not been fully understood to date. Bloating is usually associated with functional gastrointestinal disorders or organic diseases, but it may also appear alone. The pathophysiology of bloating remains ambiguous, although some evidences support the potential mechanisms, including gut hypersensitivity, impaired gas handling, altered gut microbiota, and abnormal abdominal-phrenic reflexes. Owing to the insufficient understanding of these mechanisms, the available therapeutic options are limited. However, medical treatment with some prokinetics, rifaximin, lubiprostone and linaclotide could be considered in the treatment of bloating. In addition, dietary intervention is important in relieving symptom in patients with bloating.

Use of Oral Antibiotics in Elderly Gastrointestinal Patients

Oral antibiotics are usually prescribed for geriatric patients for the treatment of infectious diarrhea and management of hepatic encephalopathy. But oral antibiotics have systemic adverse events, so many doctors face the issue of choosing the right antibiotics. Rifaximin, an intestinal topical antibiotic that exhibits a wide antimicrobial activity against both aerobic and anaerobic bacteria, has various indications, such as acute bacterial diarrhea caused by Gram positive and negative bacteria, traveler's diarrhea, small intestine bacterial overgrowth, prevention of infection after gastrointestinal surgery, and the management of hepatic encephalopathy with hyperammoniemia. But there are few clinical trial data on the geriatric population. Hence we reviewed the clinical study data that included geriatric patients in their clinical trials. Based on our literature searches, only one clinical trial on acute bacterial diarrhea was performed only for geriatric patients. Other clinical trials for various indications usually recruited elderly patients, but the number of elderly patients was limited. However, generally speaking, rifaximin showed good efficacy and safety profile in acute bacterial diarrhea caused by Gram positive and negative bacteria, traveler's diarrhea, small intestine bacterial overgrowth, prevention of infection after gastrointestinal surgery, and the management of hepatic encephalopathy with hyperammoniemia; and there were no differences in efficacy and safety, compared to the nongeriatric population. We concluded that rifaximin is a good therapeutic option for various gastrointestinal indications, and shows good efficacy and an excellent safety profile, compared to other oral agents. For more evidence on the geriatric population, we propose clinical trials on elderly patients for each indication.