Effect of rifaximin and paromomycin in the treatment of portal-systemic encephalopathy

Parini, Paolo; Cipolla, Antonio; Ronchi, M; Salzetta, Antonio; Mazzella, Giuseppe; Roda, Enrico

doi:10.1016/s0011-393x(05)80433-3

Cited by 37 publications

(40 citation statements)

References 5 publications

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“…Antibiotics with activity against urease-producing bacteria, such as neomycin [42], paromomycin [44] or metronidazole [45], also reduce the production of intestinal ammonia and have proved to be of value. Vancomycin has also been used in patients with lactulose-resistant chronic encephalopathy [46].…”

Section: Rifaximin In the Management Of Hementioning

confidence: 99%

“…Rifaximin possesses a broad spectrum of antimicrobial activity, covering Gram-positive and Gram-negative bacteria, both arerobic and anaerobic [49]. Several studies [44,[49][50][51][52][53][54][55][56][57][58][59][60][61][62] have shown that in patients with HE rifaximin displays an efficacy similar to that of lactulose and neomycin (table 1). A recently published study [62] compared the efficacy and safety of Zeneroli/Avallone/Corsi/Venturini/Baraldi/ Baraldi rifaximin to that of lactitol.…”

Section: Rifaximin In the Management Of Hementioning

confidence: 99%

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Management of Hepatic Encephalopathy: Role of Rifaximin

Zeneroli

Avallone²,

Corsi³

et al. 2005

Chemotherapy

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Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops in patients with acute or chronic liver failure. It is widely accepted to be due to impairment of hepatic clearance of toxic products from the gut such as ammonia. Accumulation of ammonia induces a glutamate neurotoxicity leading to an increased tone of the γ-aminobutyric acid A (GABA-A) receptor system in the brain which results in HE. Factors either increasing the ammonia levels (protein load, constipation, sepsis, or gastrointestinal bleeding) or potentiating the functional activity of the GABAergic system [natural benzodiazepine-like compounds (NBZDs) or exogenous benzodiazepines] may act as precipitating factors of HE. NBZDs are present in trace amounts in the blood of normal subjects and have been found to be increased in the blood of patients with liver cirrhosis, with or without HE. These compounds may derive either from the diet since they have been found in plants, vegetables and animals or from gut bacteria. The observation that intestinal bacterial flora is involved in the production of both primary agent of HE (ammonia) and precipitating factors (NBZDs) suggests that the use of nonabsorbable antibiotics such as rifaximin may be useful in preventing episodes of HE in patients with liver cirrhosis.

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Section: Rifaximin In the Management Of Hementioning

confidence: 99%

Section: Rifaximin In the Management Of Hementioning

confidence: 99%

Management of Hepatic Encephalopathy: Role of Rifaximin

Zeneroli

Avallone²,

Corsi³

et al. 2005

Chemotherapy

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“…neomycin, paromomycin) in the treatment of HE. 27,[33][34][35] In a randomized, double-blind study, rifaximin 1200 mg/ day (n = 15) was compared with neomycin 3 g/day (n = 15) in 30 patients with cirrhosis and stage 1-3 HE. 33 After 21 days of treatment, neuropsychiatric symptoms and blood ammonia concentrations were significantly reduced vs. baseline in both groups; however, reduction in blood ammonia concentrations was significantly greater with rifaximin treatment vs. neomycin.…”

Section: Comparison Of Rifaximin With Other Antibioticsmentioning

confidence: 99%

Management of Overt Hepatic Encephalopathy

Sharma

2015

Journal of Clinical and Experimental Hepatology

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Hepatic encephalopathy (HE) is an important complication of cirrhosis with significant morbidity and mortality. Management of HE primarily involves avoidance of precipitating factors and administration of various ammonia-lowering therapies such as non-absorbable disaccharides, antimicrobial agents like rifaximin and L-ornithine L-aspartate. The non-absorbable disaccharides which include lactulose and lactitol are considered the first-line therapy for the treatment of HE and in primary and secondary prophylaxis of HE. Lactitol is comparable to lactulose in the treatment of HE with fewer side effects. Rifaximin is effective in treatment of HE and recent systemic reviews found it comparable to disaccharides and is effective in secondary prophylaxis of HE. H epatic encephalopathy (HE) is a complex neuropsychiatric syndrome, which may complicate acute, chronic liver failure or patients with portal-systemic shunting. It is characterized by changes in mental state including a wide range of neuropsychiatric symptoms ranging from minor signs of altered brain function to deep coma. 1,2 It is one of the commonest indications for admission in intensive care unit in patients with advanced cirrhosis. There were over 40 000 patients hospitalized in the United States alone for a primary diagnosis of HE, resulting in total charges of approximately $932 million. Data in other countries are lacking, hence it causes a huge burden financially to the patient and society. 3 The West Haven Criteria are most often used to grade HE, with scores ranging from I-IV (IV being coma). However, it is a challenge to diagnose patients with minimal hepatic encephalopathy (MHE) or grade 1 HE; so it might be practical to combine these entities and name them covert HE for clinical use and overt HE to patients with grade II to IV. 1,4,5 One of the major tenets of the pathophysiology of HE is hyperammonemia that results from an increased nitrogenous load from the gastrointestinal tract and reduced urea synthesis both due to portal-systemic shunting and decreased urea hepatic synthesis. Brain and skeletal muscle neither remove nor produce ammonium in normal conditions, but they are able to seize ammonium during hyperammonemia, releasing glutamine. Ammonia is produced both by bacterial degradation of amines, aminoacids, purines, and urea as well as enterocytic glutaminase activity that converts glutamine to glutamate and ammonia. 6,7 Astrocytes play an important role in the pathogenesis of HE with consequences for neuronal function. Astrocytes have the ability to eliminate ammonia by the synthesis of glutamine through amidation of glutamate by the enzyme glutamine synthetase Hyperammonemia leads to the accumulation of glutamine within astrocytes, which exerts an osmotic stress that causes astrocytes to take in water and swell. 8,9 This article reviewed the clinical impact, pathogenesis, and management of overt HE in patients with cirrhosis. Articles published between January 1960 and November 2013 were acquired through a MEDLINE search of different combi...

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“…The effectiveness of rifaximin in the treatment of HE has been assessed in 16 clinical trials [47,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64]. Overall, 809 patients were involved, of whom 521 were treated with rifaximin, while 176 received disaccharides (lactulose or lactitol) and 113 with other antibiotics (neomycin, paromomycin) employed as reference drug.…”

Section: Rifaximin In the Treatment Of Hementioning

confidence: 99%

“…The early clinical studies [47,50,51,52,53,54,55,56,57,58,59,60], although not performed in GCP, have all demonstrated the good clinical efficacy and excellent tolerability of rifaximin in patients with HE, giving further support to its use in this clinical condition. A recent clinical study [63] has actually shown the efficacy of rifaximin administration in patients intolerant or non-responsive to a previous treatment with non-absorbable disaccharides.…”

Section: Rifaximin In the Treatment Of Hementioning

confidence: 99%

Management of Hepatic Encephalopathy: Focus on Antibiotic Therapy

Festi

Vestito²,

Mazzella³

et al. 2006

Digestion

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Hepatic encephalopathy (HE) is a major neuropsychiatric complication of both acute and chronic liver failure. Symptoms of HE include attention deficits, alterations of sleep patterns and muscular incoordination progressing to stupor and coma. The pathogenesis of HE is still unknown, although ammonia-induced alterations of cerebral neurotransmitter balance, especially at the astrocyte-neurone interface, may play a major role. Treatment of HE is therefore directed at reducing the production and absorption of gut-derived neurotoxic substances, especially ammonia. The non-absorbable disaccharides lactulose and lactitol were long considered as a first-line pharmacological treatment of HE, but a recent systematic review questioned their efficacy, pointing out that there is insufficient high-quality evidence to support their use. Oral antibiotics are regarded as a suitable therapeutic alternative. However, the prolonged use of antimicrobials is precluded by the possible occurrence of adverse events. Rifaximin, a synthetic antibiotic structurally related to rifamycin, displays a wide spectrum of antibacterial activity against Gram-negative and Gram-positive bacteria, both aerobic and anaerobic, and a very low rate of systemic absorption. Available evidence suggests that rifaximin – thanks to its efficacy and remarkable safety – has the highest benefit-risk ratio in the overall treatment of HE.

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Effect of rifaximin and paromomycin in the treatment of portal-systemic encephalopathy

Cited by 37 publications

References 5 publications

Management of Hepatic Encephalopathy: Role of Rifaximin

Management of Hepatic Encephalopathy: Role of Rifaximin

Management of Overt Hepatic Encephalopathy

Management of Hepatic Encephalopathy: Focus on Antibiotic Therapy

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