Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial

Miglio, F; Valpiani, D.; Rossellini,; Ferrieri, A

doi:10.1185/03007999709113333

Cited by 86 publications

(78 citation statements)

References 16 publications

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“…Current data suggests that rifaximin is as effective as established therapies like lactulose or neomycin in treatment of HE and has a better safety profile and tolerability in patients with chronic liver disease. 51,[60][61][62][63] Its' possible benefit in lowering ammonia in patients with ALF has not yet been explored.…”

Section: Ammonia Lowering Strategiesmentioning

confidence: 99%

Management in Acute Liver Failure

Shalimar

Acharya

2015

Journal of Clinical and Experimental Hepatology

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Acute liver failure (ALF) is a rare, potentially fatal complication of severe hepatic illness resulting from various causes. In a clinical setting, severe hepatic injury is usually recognised by the appearance of jaundice, encephalopathy and coagulopathy. The central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique and multifactorial. Ammonia plays a central role in the pathogenesis. The role of newer ammonia lowering agents is still evolving. Liver transplant is the only effective therapy that has been identified to be of promise in those with poor prognostic factors, whereas in the others, aggressive intensive medical management has been documented to salvage a substantial proportion of patients. A small fraction of patients undergo liver transplant and the remaining are usually treated with medical therapy. Therefore, identification of the complications and causes of death in such patients, and use of appropriate prognostic models to identify those who need liver transplant and those who can be managed with medical treatment is a vital component of therapeutic strategy. In this review, we discuss the various pathogenetic mechanisms and treatment options available. ( J CLIN EXP HEPATOL 2015;5:S104-S115)A cute liver failure (ALF) can be a fatal complication of acute hepatic injury and occurs unpredictably. It is a rare clinical entity marked by the sudden loss of hepatic function and a severe life-threatening course in a person with no prior history of liver disease. ALF represents a syndrome rather than a specific disease, having multiple causes that vary in course and outcome. ALF is difficult to identify in its early stages, resulting in frequent delays in initiation of treatment. The causes of ALF include viral hepatitis, drug induced and toxin-induced liver damage, metabolic errors, ischemia, and miscellaneous rare causes.ALF is defined by three criteria: (1) rapid development of hepatocellular dysfunction (jaundice, coagulopathy), (2) encephalopathy, and (3) absence of a prior history of liver disease. 1 However, the interval between onset of acute hepatic injury (jaundice) and onset of liver failure (encephalopathy with or without coagulopathy) in such patients (icterus-encephalopathy interval; IEI) has been described to be between 4 weeks (Indian definition) 2-4 to 24 weeks (AASLD-ALF study group). 5 Further, due to the diverse natural course, ALF has been sub-classified as hyperacute (IEI # 7 day), acute (IEI # 4 weeks) and sub-acute ALF (IEI $ 5 week to #12 weeks) by British authors. 6 Despite these differences in definitions, the central and most important clinical event in ALF is occurrence of hepatic encephalopathy (HE) and cerebral edema which is responsible for most of the fatalities in this serious clinical syndrome. The pathogenesis of encephalopathy and cerebral edema in ALF is unique an...

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Section: Ammonia Lowering Strategiesmentioning

confidence: 99%

Management in Acute Liver Failure

Shalimar

Acharya

2015

Journal of Clinical and Experimental Hepatology

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“…Rifaximin is currently used in Italy to treat enteric bacterial infection (6), small intestinal bacterial overgrowth (1), and portosystemic encephalopathy (9). Rifaximin has a broad antimicrobial spectrum that includes gram-positive and gramnegative aerobic and anaerobic bacteria (11).…”

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confidence: 99%

In Vitro Activity and Fecal Concentration of Rifaximin after Oral Administration

Jiang

Shi

Palazzini

et al. 2000

Antimicrob Agents Chemother

164

122

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Rifaximin showed moderately high MICs (the MIC at which 90% of the isolates tested were inhibited ‫؍‬ 50 g/ml) for 145 bacterial enteropathogens from patients with traveler's diarrhea acquired in Mexico during the summers of 1997 and 1998. Rifaximin concentrations in stool the day after oral administration (800 mg daily for 3 days) were high (average, 7,961 g/g), proving the value of the drug.Bacterial agents are known to be the major cause of traveler's diarrhea. It has been shown that antibacterial agents are effective in the treatment and prevention of diarrhea among persons traveling from developed to developing countries (3, 4). Rifaximin is poorly absorbed after single or repeated oral administrations to humans, even in patients with a damaged colonic mucosa (2,7,11). It is a rifamycin derivative with activity against gram-positive, gram-negative, and anaerobic bacteria (8). Recently, we evaluated rifaximin in the treatment of traveler's diarrhea. It was shown to be superior to trimethoprim-sulfamethoxazole (5) , abstr. 2227, 1999).The objectives of this study were to determine the in vitro susceptibility to rifaximin of bacterial enteropathogens isolated from cases of traveler's diarrhea and to measure rifaximin concentrations in fecal samples after oral administration.The bacterial strains used were isolates from adults who contracted traveler's diarrhea during the summers of 1997 and 1998 in Guadalajara, Mexico. The strains were identified by standard procedures and were stored at Ϫ70°C. The following numbers of strains were tested: 120 enterotoxigenic strains of Escherichia coli (ETEC), 17 Shigella strains, and 8 Salmonella strains.MICs of rifaximin for each bacterial strain were determined by agar dilution testing according to the methods of the National Committee for Clinical Laboratory Standards (10). Agar dilution plates were prepared by making a stock solution of rifaximin with acetone and preparing twofold dilutions from 200 to 0.1 g/ml. Plates with rifaximin were inoculated with 10 4 bacteria and incubated at 37°C overnight.For quality control of antimicrobial potency, the rifaximin MICs for the recommended control strains (E. coli ATCC 25922, Staphylococcus aureus ATCC 29213, and Pseudomonas aeruginosa ATCC 27853) were determined daily with the test strains. MICs were defined as the lowest concentration of rifaximin that completely inhibited visible growth. A fine, barely visible haze or a single colony was disregarded.This study was part of a large clinical trial where rifaximin was compared with ciprofloxacin in the treatment of traveler's diarrhea (DuPont et al., 39th ICAAC). Thirty-nine adult patients were included in this part of the study. All patients (Ն18 years of age) had acute diarrhea but were otherwise in good health. The patients received 400-mg tablets of rifaximin every 12 h for 3 days consecutively. They were instructed to provide the next stool passed after the 3-day treatment period. One gram of each stool sample collected posttherapy was diluted with 1 ml of solution in ace...

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“…In base ai valori misurati gli autori sono giunti alla conclusione, in accordo con quanto rilevato da precedenti studi farmacocinetici [20,[25][26][27], che la maggior parte del farmaco viene eliminata nelle feci; inoltre è stato rilevato che la concentrazione fecale di rifaximina nei cinque giorni successivi alla fine del trattamento è stata sempre superiore alla MICs delle specie batteriche isolate durante lo studio.…”

Section: Proprietà Farmacocineticheunclassified

Rifaximina nel trattamento della malattia diverticolare: potenziale terapeutico ed economico

Zaniolo

Eandi

2005

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INTRODUZIONEIl termine "malattia diverticolare" si riferisce a un concetto clinico usato a proposito di pazienti affetti da diverticolosi, sia sintomatica che asintomatica [1]. La diverticolosi del colon è una patologia acquisita caratterizzata dalla formazione di un gran numero di estroflessioni sacciformi della parete dell'intestino, localizzate più frequentemente nel colon sinistro, e in particolare nel colon sigmoideo.Queste erniazioni, dette appunto diverticoli, sono in genere causate da un'esagerata pressione all'interno del lume intestinale (diverticolo da pulsione) o, in casi limitati, da un'aderenza infiammatoria tra un organo cavo e linfonodi vicini (diverticolo da trazione). Si Rifaximina nel trattamento della malattia diverticolare: potenziale terapeutico ed economico Orietta Zaniolo*, Mario Eandi* ABSTRACTAntibiotics are commonly used to treat major inflammatory complications of diverticular disease, but apparently there is no rationale for the use of antibiotic therapy in uncomplicated disease, where an inflammatory component is by definition excluded. Some observations suggest a possible role of gut microflora in determining some symptoms related to diverticular disease: bacterial overgrowth, amplifying gas production and bacterial degradation of fibres, could determine bloating, pain and high fecal density. Therefore a beneficial antibiotic action on diverticular disease symptoms can be hypothesized. In this paper pharmacokinetic, pharmacodinamic and therapeutic potential of an intestinal antibiotic, rifaximin, are reviewed. Rifaximin is a rifamycin derivative which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. It is virtually unabsorbed after oral administration and in vitro data indicate it to possess a broad spectrum of action; bacterial resistance during exposure to rifaximin has been reported but its clinical importance remains to be fully defined. The results of placebo-controlled clinical trials show that cyclic administration of rifaximin is more effective in reducing symptoms and in preventing complications than fibre supplementation alone; the drug appears to be well tolerated and safe. We consider the clinical implications and economical impact of diverticulosis on the Italian National Health System and the patient, with a particular attention on the cost of hospitalization, surgery and global management of diverticulitis and other common disease complications. The hypothetic savings correlated to the reduction of complications incidence, attainable with rifaximin use have been calculated and the comparison between the different acquisition costs of the drug frequently used to treat the diverticular disease is provided. Finally we reviewed some quality of life trials in which the psychological and sociological influence of the disease symptoms and treatments on the patient are assessed.Keywords: diverticular disease, rifaximin, antibiotics, economical impact Farmeconomia e percorsi terapeutici 2005; 6 (1): 5-20 PROFILO *Farmacologia Clinica, Università di Torino rit...

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Rifaximin, a non-absorbable rifamycin, for the treatment of hepatic encephalopathy. A double-blind, randomised trial

Cited by 86 publications

References 16 publications

Management in Acute Liver Failure

Management in Acute Liver Failure

In Vitro Activity and Fecal Concentration of Rifaximin after Oral Administration

Rifaximina nel trattamento della malattia diverticolare: potenziale terapeutico ed economico

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