Rifaximin therapy and hepatic encephalopathy: Pros and cons.

August 2912

Zullo A, Hassan C, Ridola L, Lorenzetti R, Campo SM, Riggio O.

Source

Angelo Zullo, Cesare Hassan, Roberto Lorenzetti, Salvatore MA Campo, Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita Hospital, 00153 Rome, Italy.

Abstract

Hepatic encephalopathy (HE) is the second most common major complication in cirrhotics and it significantly impacts quality of life. Therapeutic approaches for HE treatment and prevention mainly continue to rely on ammonia-lowering strategies and non-absorbable disaccharides are currently considered the cornerstone therapy. Non-absorbable antibiotics, such as neomycin and paramomycin, are effective in treatment of acute HE episodes but their prolonged use for recurrence prevention is hampered by possible side-effects. To overcome these limitations, rifaximin use has been proposed. Rifaximin has been shown to be not superior to non-absorbable disaccharides for either HE treatment or prevention, with a similar incidence of side-effects. Cirrhosis significantly increases rifaximin absorption and this could be a cause for concern. Following long-term rifaximin therapy, Clostridium difficile colitis has been observed and Candida albicans has been isolated from 20% of patients. In addition, selection of resistant mutants of both Gram-negative and -positive bacteria in the gastrointestinal tract cannot be definitely ruled out. Electrolyte alterations (sodium and potassium) have been reported during rifaximin therapy, a warning for its long-term use in cirrhotics. Moreover, a potential interference with vitamin K production should be considered which could further impair the already altered clotting status of these patients. The therapeutic cost of rifaximin is markedly higher than non-absorbable disaccharides. While waiting for further safety data, caution should be used to limit the use of rifaximin therapy for a very short-term period in selected HE cirrhotics not responding to non-absorbable disaccharides.

PubMed

Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.

Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.

J Antimicrob Chemother. 2007 Mar 2;

Musher DM,
Logan N,
Mehendiratta V,
Melgarejo NA,
Garud S,
Hamill RJ.
Medical Service (Infectious Disease Section), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.

Objectives Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. Methods In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >/=14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. Results Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). Conclusions Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.

PMID: 17337513 [PubMed - as supplied by publisher]