Rifaximin therapy

In addition to ANP where it is associated with GI dys-motility [198, 199], SIBO is present in a significant proportion of patients with chronic pancreatitis [200, 201], Short-term rifaximin therapy was able to normalize the hydrogen breath test and improve symptoms (i.e. diarrhea and fecal fat excretion) in all patients studied (fig. 9) [201]. Bowel decontamination via administration of this topical antibiotic could, therefore, be beneficial in both acute and chronic pancreatitis. Double-blind, placebo-controlled studies are to be performed to explore the rifaximin potential in this indication. 

Stornello and Slanitri [29] 50% reduction in stool frequency between day 3 and 4 in both treatment groups oral rifaximin therapy discontinued in 1 child due to vomiting 90%... 

Infante RM, Ericsson CD, Jiang ZD, Ke S, Steffen R, Riopel L, Sack DA, DuPont HL Enteroaggregative Escherichia coli diarrhea in travelers Response to rifaximin therapy. Clin Gastroenterol Hepatol 2004 2 135-138. 

Antibiotics like neomycin or metronidazole are administered either when an episode of HE arises or chronically to avoid the development of clinically overt HE. In the past, neomycin was the most used antibiotic. There is increasing evidence, however, that rifaximin has a more favorable benefit risk ratio in the treatment of HE (Leevy and Phillips, 2007 Mas et al., 2003). While neuro- and nephrotoxicity have to be considered in neomycin rifaximin is well-tolerated. Recently Leevy and Phillips (2007) showed in 145 patients that the frequency and grade of HE was lower with rifaximin therapy compared to lactulose therapy, and that with rifaximin therapy the patients were less often hospitalized than with lactulose. 

DuPont HL, Ericsson CD, Mathewson JJ, Palazzini E, DuPont MW, Jiang ZD, Mosavi A, de la Cabada FJ Rifaximin A nonab-sorbed antimicrobial in the therapy of travelers diarrhea. Digestion 1998 59 708-714. 

Antimicrobial resistance to rifamycins develops rapidly both in vitro and in vivo [65,85,86], As a consequence, all the three members of the family (i.e. rifampicin, rifabutin and rifapentine) are used clinically as components of combination therapies [65,87], Being structurally related, rifaximin could share this potential. And indeed resistance rates, recorded in fecal strains of Enterobacteriaceae, Enterococcus, Bacteroides, Clostridium and anaerobic cocci, ranged between 30 and 90% after short-term (5 days) antibiotic (800 mg daily) treatment [82], A similar pattern was observed in 10 patients with hepatic encephalopathy after treatment with rifaximin 1,200 mg/day for 5 days [80]. 

As shown in table 7, there are established and potential clinical indications for this peculiar drug. In all these conditions, many of which share SIBO as a common feature, gut bacteria represent the specific target of rifaximin. The drug can be used alone (like, for instance, in the treatment of infectious diarrhea) or as add-on medication (as in the management of IBD) and given short-term (single course of treatment) or long-term (repeated courses of therapy, i.e. cyclically). 

Steffen R, Sack DA, Riopel L, Jiang ZD, Sturchler M, Ericsson CD, Lowe B, Waiyaki P, White M, DuPont HL Therapy of travelers diarrhea with rifaximin on various continents. Am J Gastroenterol 2003 98 1073-1078. 

The available data suggest that bacterial resistance does not seem to be a major concern of the therapy with rifaximin. However, further monitoring of the occurrence of bacterial resistance to rifaximin would help to clearly define its clinical importance. 

Vinci M, Gatto A, Giaglio A, Raciti T, D Avola G, Di Stefano B, Salanitri G, Di Stefano F Double-blind clinical trial on infectious diarrhea therapy Rifaximin versus placebo. Curr TherRes Clin Exp 1984 36 92-99. 

An increasing number of both clinical and laboratory-derived observations support the importance of luminal components in driving the inflammatory response in ulcerative colitis and Crohn s disease. Although its role is unclear, antibiotic therapy is commonly used in clinical practice for the treatment of moderately to severely active ulcerative colitis. Metronidazole and/or ciprofloxacin are currently employed in active Crohn s disease, particularly in patients with colonic involvement and with perianal disease. Rifaximin, a rifamycin-derived antibiotic, is characterized by a wide range of antibacterial activity and a very low systemic absorption. Some preliminary data show its efficacy in severe active ulcerative colitis, pouchitis and prevention of postoperative recurrence in Crohn s disease. 

A first open, uncontrolled study [46], performed in 12 patients with active IBD refractory to standard treatment who all had positive stool culture, suggested that adding rifaximin (800 mg daily) could be beneficial. A further small but controlled investigation performed in our unit [47] evaluated the efficacy and systemic absorption of rifaximin in patients with moderately to severely active UC refractory to steroid treatment. Patients were eligible if they had no response to intravenous corticosteroid therapy (methylprednisolone 1 mg/kg/day) after 7-10 days. Twenty-eight patients were randomized to receive rifaximin 400 mg b.i.d. or placebo for 10 days as an add-on... 

Table 1. Rifaximin vs. placebo in severe UC outcome after 10 days of therapy (from Gionchetti et al. [47])...

Pinto A, Borrutto G, Deall Anna A, Turco L, Ferried A An open, uncontrolled trial of oral rifaximin, a non-absorbable antibiotic, in inflammatory bowel disease refractory to conventional therapy. Eur J Clin Res 1997,9 217-224. 

Rifaximin Small intestine bacterial overgrowth Therapy Nonabsorbable antibiotics... 

Fig. 1. Fasting, peak and total breath H2 excretion before and after rifaximin or chlortetracycline therapy in two groups of patients with SIBO (from Di Stefano et al. [42]). NS = Not significant.

A significant improvement of symptom severity and the absence of side effects was also evident after rifaximin administration but not after tetracycline, reinforcing, therefore, the validity of the therapeutic approach adopted. Rifaximin has proved to be effective in the treatment of gas-related symptoms in fact, in a recent paper, it was reported that a 7-day course of therapy significantly improved the severity of symptoms in a cohort of patients... 

Another recent controlled trial showed a good therapeutic effect of both amoxicillin-clavulanic acid and norfloxacin in SIBO patients [45]. However, a rapid relapse of diarrhea just few days after the withdrawal of antibiotics was evident. In this paper, the efficacy of probiotics in SIBO patients was also evaluated, but no significant effect was described. While on the one hand these results confirm the frequent need of several courses of antibiotic therapy in SIBO patients, on the other they support the idea that rifaximin may represent a good choice on the basis of its excellent tolerability. 

Double blind clinical trial on infectious diarrhoea therapy Rifaximin versus placebo. Curr Ther Res 1984 36 92-99. 

Rifaximin Rifamycin Antibiotic therapy Skin infections Vaginosis, bacterial Periodontal disease... 

Non-absorbable disaccharides such as lactulose and lactitol are still routinely used to deoease ammonia production in the gut despite a lack of adequate controlled clinical trials. In the case of lactulose, the ammonia-lowering effect appears to involve increased fecal nitrogen excretion by facilitation of the incorporation of ammonia into bacteria as well as a cathartic effect. Antibiotics such as neomycin have ttaditionaUy been used to lower blood ammonia by inhibition of ammonia production by intestinal bacteria. However, neomycin therapy is associated with significant toxic side effects and is increasingly being replaced by alternative antibiotics such as rifaximin. 

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