rifaximin and Diarrhea

Prulifloxacin, the prodrug of ulifloxacin (active component), is a newer fluoroquinolone with broad activity against enteric and nonenteric gram-negative bacilli. Ulifloxacin and other oral comparator agents were tested for activity against 582 gastroenteritis strains from global surveillance studies. Ulifloxacin was highly active against Escherichia coli, Salmonella spp., Shigella spp., Yersinia spp., Vibrio spp., Aeromonas spp., and Plesiomonas spp. (MIC(50)s and MIC(90)s, or=4 microg/ml). Ciprofloxacin exhibited similar activity but was two- to fourfold less potent. Presently approved for clinical use in certain European countries and Japan, ulifloxacin was the most active of the antimicrobial agents tested against these gastroenteritis-causing pathogens.

Topics: Anti-Bacterial Agents; Diarrhea; Dioxolanes; Fluoroquinolones; Gastroenteritis; Gram-Negative Bacteria; Humans; Piperazines; Population Surveillance; Prodrugs

Clostridium difficile-associated colitis is an increasing cause of morbidity and mortality in hospitalized patients, with high relapse rates following conventional therapy. We sought to determine the efficacy of rifaximin, a novel nonabsorbed antibiotic, in the hamster model of C. difficile-associated diarrhea (CDAD). Hamsters received clindamycin subcutaneously and 24 h later were infected by gavage with one of two C. difficile strains: a reference strain (VPI 10463) and a current epidemic strain (BI17). Vancomycin (50 mg/kg of body weight) or rifaximin (100, 50, and 25 mg/kg) were then administered orally for 5 days beginning either on the same day as infection (prevention) or 24 h later (treatment). Therapeutic effects were assessed by weight gain, histology, and survival. We found that rifaximin was as effective as vancomycin in the prevention and treatment of colitis associated with the two C. difficile strains that we examined. There was no relapse after treatment with vancomycin or rifaximin in hamsters infected with the BI17 strain. Hamsters infected with the VPI 10463 strain and treated with rifaximin did not develop relapsing infection within a month of follow-up, whereas the majority of vancomycin-treated animals relapsed (0% versus 75%, respectively; P < 0.01). In conclusion, rifaximin was found to be an effective prophylactic and therapeutic agent for CDAD in hamsters and was not associated with disease recurrence. These findings, in conjunction with the pharmacokinetic and safety profiles of rifaximin, suggest that it is an attractive candidate for clinical use for CDAD.

Topics: Animals; Anti-Infective Agents; Clostridioides difficile; Cricetinae; Diarrhea; Enterocolitis, Pseudomembranous; Humans; Mesocricetus; Rifamycins; Rifaximin; Treatment Outcome; Vancomycin; Weight Gain

Diarrhea in children is often caused by enteropathogen infections that might benefit from early empirical antibiotic therapy. However, when the definition of the pathogen requires sophisticated laboratory studies, the etiology of enteritis is not known early in illness. Empirical therapy may be dangerous if the child is infected with a Shiga toxin-producing Escherichia coli (STEC) strain because antimicrobials may increase Shiga toxin (Stx) release, resulting in increased risk of microangiopathic hemolytic anemia with acute renal failure (hemolytic-uremic syndrome [HUS]) and death. There is a need for antimicrobials that would be effective against multiple bacterial enteropathogens yet not induce Stx release or increase the risk of HUS. Rifaximin has been evaluated in adults for treatment of bacterial enteritis and has a good record for safety and efficacy, but it has not been evaluated extensively in children with gastroenteritis. We therefore evaluated rifaximin's potential for phage induction, drug-induced bacteriolysis, and toxin release in 57 STEC strains (26 O157 and 31 non-O157 strains). Growth in ciprofloxacin, a known Stx phage inducer, caused bacteriolysis and release of toxin in 25/26 (96%) O157 strains and 15/31 (48%) non-O157 strains. In contrast, rifaximin did not induce phage replication or lysis in any strain. Toxin release in the presence of rifaximin was not different from release in the absence of antibiotic. Rifaximin, unlike many antibiotics used to treat pediatric gastroenteritis, does not induce phage-mediated bacteriolysis and Stx release.

Topics: Anti-Infective Agents; Bacteriolysis; Child; Child, Preschool; Coliphages; Diarrhea; Escherichia coli; Escherichia coli Infections; Escherichia coli O157; Hemolytic-Uremic Syndrome; Humans; Lysogeny; Rifamycins; Rifaximin; Shiga Toxins; Virus Activation