Experimental and Clinical Pharmacology of Rifaximin, a Gastrointestinal Selective Antibiotic

Abstract

Rifaximin (4-deoxy-4′-methylpyrido[1′,2′-1,2]imidazo [5,4-c]rifamycin SV) is a product of synthesis experiments designed to modify the parent compound, rifamycin, in order to achieve low gastrointestinal (GI) absorption while retaining good antibacterial activity. Both experimental and clinical pharmacology clearly show that this compound is a non-systemic antibiotic with a broad spectrum of antibacterial action covering Gram-positive and Gram-negative organisms, both aerobes and anaerobes. Being virtually non-absorbed, its bioavailability within the GI tract is rather high with intraluminal and fecal drug concentrations that largely exceed the minimum inhibitory concentration values observed in vitro against a wide range of pathogenic organisms. The GI tract represents therefore the primary therapeutic target and GI infections the main indication. This antibiotic has therefore little value outside the enteric area and this will minimize both antimicrobial resistance and systemic adverse events. Indeed, the drug proved to be safe in all patient populations, including young children. The appreciation of the pathogenic role of gut bacteria in several organic and functional GI diseases has increasingly broadened its clinical use, which is now extended to hepatic encephalopathy, small intestine bacterial overgrowth, inflammatory bowel disease and colonic diverticular disease.

Impact of rifaximin on the frequency and characteristics of spontaneous bacterial peritonitis in patients with liver cirrhosis and ascites

“…However, the observed clinical improvement of HE suggests good adherence in the studied patient cohort. In addition, the biological intestinal half time of rifaximin is several days [9,39] and consequently even the omission of one or two dosages would not result in insufficient drug levels. Future studies on the effects of rifaximin on SBP should include assessment of bacterial resistance to rifaximin, which is complicated by the unavailability of commercially available resistance tests or standardized testing procedures with normal values.…”

Advances in the management of colonic diverticulitis: Figure 1:

“…and anaerobic cocci) recovers within 1-2 weeks after the end of treatment. 27 Thus, repeated oral administration of rifaximin may control the colonic bacterial population for only 15-20 days, with higher colonic bacterial concentrations for the last 10 days of the month, therefore leading to a higher risk of recurrence. There is no evidence to support the use of other antibiotic regimens for the prevention of diverticulitis recurrence.…”

Pharmacotherapy of hepatic encephalopathy in cirrhosis

“…Rifaximin is a semi-synthetic, non-systemic antibiotic derivative of rifamycin with a wide spectrum of antimicrobial activity and low gastrointestinal absorption (0.5%) and, as such, has almost no adverse effects and no resistance develops [21]. Rifaximin inhibits RNA synthesis and shows antibacterial activity against Gram-positive and Gram-negative bacteria, aerobes and anaerobes.…”