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

Brown, Eric L.; Xue, Qiong; Jiang, Zhi‐Dong; Xu, Yi; DuPont, Herbert L.

doi:10.1128/aac.00691-09

Cited by 89 publications

(65 citation statements)

References 28 publications

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“…Moreover, other effects of these antibiotics, e.g., the extent to which they reduce the normal intestinal flora or their influence on intestinal adherence of the pathogen, might modulate the course of EHEC infection. Indeed, reduced adherence to epithelial cells after their pretreatment with rifaximin has been reported for EAEC (5). Finally, thorough analyses of clinical outcomes of patients who were administered these antibiotics during the outbreak are necessary for ultimate evaluation of their potential usefulness for treatment of humans infected with EHEC O104:H4 in cases where antibiotic therapy is inevitable.…”

Section: Discussionmentioning

confidence: 99%

Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain

Bielaszewska

Idelevich

Zhang

et al. 2012

Antimicrob Agents Chemother

170

144

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ABSTRACTThe role of antibiotics in treatment of enterohemorrhagicEscherichia coli(EHEC) infections is controversial because of concerns about triggering hemolytic-uremic syndrome (HUS) by increasing Shiga toxin (Stx) production. During the recent large EHEC O104:H4 outbreak, antibiotic therapy was indicated for some patients. We tested a diverse panel of antibiotics to which the outbreak strain is susceptible to interrogate the effects of subinhibitory antibiotic concentrations on induction ofstx2-harboring bacteriophages,stx2transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increasedstx2-harboring phage induction and Stx2 production in outbreak isolates (Pvalues of <0.001 to <0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (P> 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (P≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulatedstx2transcription, respectively (P< 0.01); the other antibiotics had insignificant effects (P> 0.1). Meropenem, azithromycin, and rifaximin, which were used for necessary therapeutic or prophylactic interventions during the EHEC O104:H4 outbreak, as well as tigecycline, neither inducedstx2-harboring phages nor increasedstx2transcription or Stx2 production in the outbreak strain. These antibiotics might represent therapeutic options for patients with EHEC O104:H4 infection if antibiotic treatment is inevitable. We await further analysis of the epidemic to determine if usage of these agents was associated with an altered risk of developing HUS.

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Section: Discussionmentioning

confidence: 99%

Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain

Bielaszewska

Idelevich

Zhang

et al. 2012

Antimicrob Agents Chemother

170

144

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“…21 Rifaximin and rifamycin SV have been shown to affect epithelial cell physiology, induce changes in bacterial attachment/internalization, and reduce inflammatory cytokine release. 11,12,20,22,23 These factors may all reduce pathogen virulence and contribute to clinical improvements at time points when the pathogen can still be detected in the stools. If bactericidal effects alone explained the clinical response we would have expected efficient eradication of the pathogens from the gut lumen.…”

Section: Discussionmentioning

confidence: 99%

Targeting of Rifamycin SV to the Colon for Treatment of Travelers' Diarrhea: A Randomized, Double‐Blind, Placebo‐Controlled Phase 3 Study

DuPont¹,

Petersen²,

Zhao

et al. 2014

J Travel Med

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Background. Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, Rifamycin SV MMX ® (RIF-MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a unique rifamycin drug. Methods. This was a randomized, double-blind, phase 3 study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A total of 264 patients received RIF-MMX (2 × 200 mg twice daily for 3 days, n = 199) or placebo (n = 65) in a 3 : 1 ratio. The primary endpoint was the length of time between the administration of first dose of study drug and passage of the last unformed stool (TLUS; after which clinical cure was declared). Other endpoints included eradication of pathogens from the stools, pathogen minimum inhibitory concentration (MIC), and adverse events (AEs). Results. TLUS was significantly shorter in the RIF-MMX group (median: 46.0 hours) compared with placebo (median: 68.0 hours; p = 0.0008) and a larger percentage of RIF-MMX treated patients (81.4%) achieved clinical cure compared with placebo patients (56.9%). TLUS was significantly shorter in the subgroups of patients with enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli infections (p = 0.0035) with nonsignificant activity against invasive bacteria (p = 0.3804). Overall pathogen eradication rates were numerically higher in the RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not reach significance (p = 0.0836). In vitro resistance to rifamycin SV was observed in some bacteria remaining after treatment of patients with RIF-MMX but was not associated with lower efficacy in them. AEs appeared to be more frequent with placebo (38.5%) than with RIF-MMX (29.6%). Conclusions. RIF-MMX shortened the duration of TD in patients with a broad range of pathogens and was well tolerated. The unique pharmacokinetic properties of the drug offer evidence that TD pathogens work at the level of the colon.

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“…11 In addition, it modulates intestinal inflammation by reducing the expression of bacterial virulence factors, adhesion and epithelial internalization of pathogens and inflammatory cytokine production. [21][22][23] It has been reported that rifaximin is able to modulate intestinal Figure 3. OS within the first 12 months after ASCT in relation to the type of gut decontamination.…”

Section: Discussionmentioning

confidence: 99%

Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation

Weber

Oefner

Dettmer

et al. 2016

Bone Marrow Transplant

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Intestinal dysbiosis has been associated with acute gastrointestinal GvHD and poor outcome following allogeneic stem cell transplantation (ASCT). To assess the effect of a switch in 2012 from ciprofloxacin/metronidazole to rifaximin for gut decontamination on intestinal microbiota composition and ASCT outcome, we retrospectively analyzed 394 patients receiving ASCT from September 2008 through June 2015. In 131 and 90 patients, respectively, urinary 3-indoxyl sulfate levels and intestinal enterococcal load were measured before conditioning and weekly within the first 28 days after ASCT. The use of rifaximin correlated with lower enterococcal positivity (6.9 vs 21.9%, P = 0.05) and higher urinary 3-indoxyl sulfate concentrations (10.5 vs 4.6 μmoL/mmoL crea, P o0.001) after ASCT. Patients on rifaximin showed lower 1-year transplant-related mortality (P = 0.04) and higher overall survival (P = 0.008). Treatment of infectious complications with systemic antibiotics did not abrogate the beneficial effects of rifaximin on intestinal microbiota composition in the early course of ASCT and outcome. The data underscore the importance of maintaining a diverse population of symbiotic and mutualistic bacteria in the gut on ASCT outcome.

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

Cited by 89 publications

References 28 publications

Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain

Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain

Targeting of Rifamycin SV to the Colon for Treatment of Travelers' Diarrhea: A Randomized, Double‐Blind, Placebo‐Controlled Phase 3 Study

Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation

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