Effects of Rifaximin on Bacterial Virulence Mechanisms at Supra- and Sub-Inhibitory Concentrations

Abstract

Rifaximin, a poorly absorbed rifamycin derivative, exhibited time-dependent bactericidal activity and at concentrations as low as 1/32 of the minimum inhibitory concentration (MIC) caused morphological alterations in both susceptible and resistant bacterial strains. Spontaneous rifaximin-resistant clones appeared with an incidence of 2.6 x 10(-7). The percentage of Escherichia coli cells cured of various plasmids ranged from: 4.5-70% (Flac), 0-18% (pBP507), 7.7-43.8% (plasmid carrying ESBL genes) and 22.4-41.6% (plasmid encoding toxin from ETEC mex264). 8.4-18.2 and <0.1-18% of Staphylococcus aureus cells were cured (plasmid-mediated penicillinase), 9.5-58.6% of Morganella morganii (ESBL), 10.6-47.1% Citrobacter freundii (ESBL), 2.3-38.7% of Proteus mirabilis (ESBL) and 14.3-66.6% of Klebsiella pneumoniae (ESBL). Rifaximin reduced plasmid transfer from donor to recipient strains by >99%. The MIC of ceftazidime was reduced (2-4 dilutions) in the presence of rifaximin (0.5 x MIC) in ESBL producing strains. Rifaximin lowered the viability and virulence of the bacteria even though they developed resistance to the compound. In conclusion, the present findings add new features to the microbiological characteristics of rifaximin and suggest that if in vivo pathogens are exposed to sub-MICs of the drug, not only are their physiological functions compromised, but gene virulence and antibiotic resistance are not fully expressed.

Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells

“…Rifaximin is a poorly absorbed oral antimicrobial agent that is concentrated in the gastrointestinal tract [33][34][35]. Rifaximin has a broad-spectrum of activity against gram-positive and gram-negative aerobic and anaerobic enteric bacteria [36][37][38].…”

New and emerging therapies for the treatment of irritable bowel syndrome: an update for gastroenterologists

“…The nonsystemic antibiotic rifaximin appears to have anti-inflammatory, host-response, and gut microbiota modulatory activities [Bajaj et al 2013;Brown et al 2010;Cheng et al 2010;Debbia et al 2008;DuPont and Jiang, 2004;Hopkins et al 2014;Jiang et al 2010aJiang et al , 2010bMaccaferri et al 2010;Mencarelli et al 2010Mencarelli et al , 2011Schrodt et al 2013;Terc et al 2014;Xu et al 2014]. Rifaximin received regulatory approval for the treatment of IBS-D in May 2015; several studies indicated a favorable efficacy and safety profile for rifaximin in IBS-D (Table 3) [Di Stefano et al 2011;Pimentel et al 2006Pimentel et al , 2011Pimentel et al , 2014.…”

Pretreatment of Epithelial Cells with Rifaximin Alters Bacterial Attachment and Internalization Profiles

“…The HEp-2 cell attachment assay was carried out as described previously (11), except that confluent monolayers were used instead of cells grown to 50 to 80% confluence unless otherwise specified. HEp-2 cells were grown in Lab-Tek II (Nunc, Rochester, NY) chambered slides and were incubated in the presence of antibiotics or the appropriate controls for 4,8,16,18, and 24 h. At the end of the antibiotic incubation period, chambers were washed three times with PBS (phosphate-buffered saline, pH 7.4) prior to the addition of EAEC (7 ϫ 10 6 to 1 ϫ 10 7 bacteria in 1 ml DMEM, 10% FBS, and 1% D-mannose) (2, 9) that had been cultured at 37°C overnight in Trypticase soy broth (Difco, Lawrence, KS) with 1% D-mannose (Sigma, St. Louis, MO). After a 3-h incubation at 37°C, the attachment of E. coli O42 to epithelial cells was visualized microscopically following Wright-Giemsa staining (Protocol Hema 3; Fisher Diagnostics, Middletown, VA) using an Olympus BX60 inverted microscope attached to an Olympus C-5060 digital camera.…”