In Vitro Activity and Fecal Concentration of Rifaximin after Oral Administration

Abstract

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...

Sulfate-reducing bacteria of the human intestine. II. The role in the diseases development

“…Рифаксимін не адсорбується кишечником [11,42,88,109], тому його виявляють у фекаліях у високих концентраціях [46]. Діє на грампозитив-ні та грамнегативні бактерії товстої кишки [88,109].…”

“…Діє на грампозитив-ні та грамнегативні бактерії товстої кишки [88,109]. Цей антибіотик активний щодо бактерій E. coli, представників родів Salmonella і Shigella, тому, як і ципрофлокса-цин, його застосовують для лікування діареї [46,103].…”

Rifaximin for the treatment of acute infectious diarrhea

“…In addition, a pharmacokinetic study reported an extremely high fecal concentration of rifaximin after oral ingestion [Jiang et al 2000]. Nevertheless, the in vivo effect of rifaximin was disappointing in patients in whom invasive pathogen(s) were isolated [Taylor et al 2006].…”

“…When radiolabeled rifaximin was administered orally, the bioavailability of rifaximin was less than 0.4% in the blood and urine, and 97% was recovered unchanged in stool [Descombe et al 1994]. After the oral administration of 400 mg rifaximin twice a day for three days to travelers with diarrhea, its fecal level reached extremely high concentrations up to the range of 40008000 mg/g [Jiang et al 2000].…”

“…An extensive microbiological survey demonstrated that the minimum inhibitory concentration for 90% of microorganism growth (MIC 90 ) ranged from 4 to 64 mg/ml for enteric pathogens isolated from stool specimens from travelers' diarrhea patients spanning three continents, including the enterotoxigenic E. coli (ETEC) and EAEC, Salmonella, Shigella, Campylobacter, Plesiomonas, and Aeromonas species [Gomi et al 2001;Jiang et al 2000]. Other studies have confirmed similar bacterialsusceptibility patterns showing the broad spectrum of antimicrobial action, covering Gram-positive and Gram-negative and both aerobes and anaerobes [Ruiz et al 2007;Sierra et al 2001aSierra et al , 2001b.…”