Rifaximin dose‐finding study for the treatment of small intestinal bacterial overgrowth

Lauritano, Ernesto Cristiano; Gabrielli, Maurizio; Lupascu, A.; Santoliquido, Angelo; Nucera, Gabriella; Scarpellini, Emidio; Vincenti, F.; Cammarota, Giovanni; Flore, Roberto; Pola, Paolo; Gasbarrini, Giovanni; Gasbarrini, Antonio

doi:10.1111/j.1365-2036.2005.02516.x

Cited by 108 publications

(90 citation statements)

References 18 publications

(24 reference statements)

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“…The GI tract can also contain substantial amounts of H 2 (38). Bacteria were grown in pH-and temperature-regulated bioreactors using glucose as the sole and limiting carbon source (pH 7, 37°C, 30 mM glucose).…”

Section: Analysis Of Central Carbon Metabolism In Early Grown Bmentioning

confidence: 99%

Restricting Fermentative Potential by Proteome Remodeling

Clair¹,

Armengaud²,

Duport³

2012

Molecular & Cellular Proteomics

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Pathogenesis hinges on successful colonization of the gastrointestinal (GI) tract by pathogenic facultative anaerobes. The GI tract is a carbohydrate-limited environment with varying oxygen availability and oxidoreduction potential (ORP). How pathogenic bacteria are able to adapt and grow in these varying conditions remains a key fundamental question. Here, we designed a system biologyinspired approach to pinpoint the key regulators allowing Bacillus cereus to survive and grow efficiently under low ORP anoxic conditions mimicking those encountered in the intestinal lumen. We assessed the proteome components using high throughput nanoLC-MS/MS techniques, reconstituted the main metabolic circuits, constructed ⌬ohrA and ⌬ohrR mutants, and analyzed the impacts of ohrA and ohrR disruptions by a novel round of shotgun proteomics. Our study revealed that OhrR and OhrA are crucial to the successful adaptation of B. cereus to the GI tract environment. Specifically, we showed that B. cereus restricts its fermentative growth under low ORP anaerobiosis and sustains efficient aerobic respiratory metabolism, motility, and stress response via OhrRA-dependent proteome remodeling. Finally, our results introduced a new adaptive strategy where facultative anaerobes prefer to restrict their fermentative potential for a long term benefit. Molecular & Cellular Proteomics 11: 10.1074/ mcp.M111.013102, 1-13, 2012.Facultative anaerobes encompass all the major pathogens of the human gastrointestinal (GI) 1 tract. The GI tract poses several challenges for pathogens because it is sliced into distinct niches with different oxygen concentrations and different oxidoreduction potentials (ORP) (1-3). Although much is known about gene expression and metabolism under fully aerobic and high ORP anaerobic condition (4, 5), our knowledge about the physiological impact of low ORP anoxic conditions and the underlying molecular mechanisms is scarce (6).Bacillus cereus is a notorious food-borne pathogenic bacterium. Like the closely related Bacillus anthracis (7,8), it is a recognized agent of GI tract infections (9 -11). The critical step of infection takes place in the small intestine, where B. cereus has to grow and produce virulence factors to induce diarrheal disease (11, 12). Thus, how B. cereus adapts its catabolism and regulates its proteome across the range of physiologically relevant ORP and oxygen availabilities is important for its survival and growth. In B. cereus, anaerobic and aerobic catabolism work through different pathways. In the presence of oxygen, reducing equivalents generated by glycolysis and the TCA cycle (NADH and FADH) are reoxidized by the respiratory chain, resulting in the buildup of a proton motive force and the subsequent synthesis of ATP. Acetate excretion can occur aerobically when carbon flux into the cells exceeds TCA cycle capacity. In the absence of oxygen or other external electron acceptors (such as nitrate), NADH is reoxidized in terminal step fermentative reactions from pyruvate. When grown in pH-controlled ana...

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Section: Analysis Of Central Carbon Metabolism In Early Grown Bmentioning

confidence: 99%

Restricting Fermentative Potential by Proteome Remodeling

Clair¹,

Armengaud²,

Duport³

2012

Molecular & Cellular Proteomics

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“…In a recent dose-finding study [61], performed to assess the efficacy of rifaximin in the treatment of small intestine bacterial overgrowth (SIBO), it was found that 70% of these patients were H. pylori -positive. This observation gave the opportunity to evaluate simultaneously the disappearance of SIBO and the eradication of the microorganism.…”

Section: In Vivo Helicobacter Pylori Eradication Trialsmentioning

confidence: 99%

“…1 Rifaximin dose-response curves for decontamination of SIBO (y = –13.571 + 6.6429e-2x, r 2 = 1.000) and eradication of H. pylori (y = –6.5714 + 3.1429e-2x, r 2 = 0.910) in the same (n = 63 out of 90) patients (from data in Lauritano et al [61] and unpublished data by the same authors). …”

Section: In Vivo Helicobacter Pylori Eradication Trialsmentioning

confidence: 99%

Eradication of <i>Helicobacter pylori</i>: Are Rifaximin-Based Regimens Effective?

Gasbarrini

Pelosini

et al. 2006

Digestion

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Rifaximin is a non-absorbed semisynthetic rifamycin derivative with a broad spectrum of antibacterial activity including Gram-positive and Gram-negative bacteria, both aerobes and anaerobes. Although originally developed for the treatment of infectious diarrhea, the appreciation of the pathogenic role of gut bacteria in several organic and functional gastrointestinal diseases has increasingly broadened its clinical use. Being the antibiotic active against Helicobacter pylori, even towards clarithromycin-resistant strain, and being the primary resistance very rare, several investigations explored its potential use for eradication of the microorganism. Rifaximin alone proved to be effective, but even the highest dose (1,200 mg daily) gave a cure rate of only 30%. Dual and triple therapies were also studied, with the better results obtained with rifaximin-clarithromycin and rifaximin-clarithromycin-esomeprazole combinations. However, the eradication rates (60–70%) obtained with these regimens were still below the standard set by the Maastricht Consensus guidelines. Although rifaximin-based eradication therapies are promising, new antimicrobial combinations (with and without proton pump inhibitors) need to be explored in well-designed clinical trials including a large cohort of H. pylori-infected patients. The remarkable safety of rifaximin will allow high-dose regimens of longer duration (e.g. 10 or 14 days) to be tested with confidence in the hope of achieving better eradication rates. A drawback of rifaximin could be its inability to reach sufficiently high concentrations in the gastric mucus layer under and within which H. pylori is commonly located and this would likely affect eradication rate. Taking these considerations into account, bioadhesive rifaximin formulations able to better and persistently cover gastric mucosa, or combination with mucolytic agents, such as pronase or acetylcysteine, need to be evaluated in order to better define the place of this antibiotic in our therapeutic armamentarium.

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“…Since rifaximin was found to be active against H. pylori strains resistant to clarithromycin [31] , it was speculated that this antibiotic could be associated in vivo with this antimicrobial [26] . In a previous investigation [24] , it was shown that monotherapy with rifaximin provides an eradication rate of 37%, that is substantially higher than previously reported for single antimicrobial therapy (with the exception of clarithromycin). The association in a dual regimen with other antimicrobial drugs achieved an eradication rate ranging from 40% in association with colloidal bismuth subcitrate to 62% in association with metronidazole [29] .…”

Section: Discussionmentioning

confidence: 69%

“…Moreover, there is increasing evidence suggesting that rifaximin represents an effective treatment option for small intestinal bacterial overgrowth [23,24] .…”

Section: Introductionmentioning

confidence: 99%

Rifaximin-Based Regimens for Eradication of <i>Helicobacter pylori</i>: A Pilot Study

Gasbarrini

Lauritano

Nista

et al. 2006

Dig Dis

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Background: Triple therapy is the treatment of choice for Helicobacter pylori-infected patients with an eradication rate ranging from 70 to 85%. Poor compliance and antibiotic resistance are the main causes of treatment failure. The aim of the present study was to assess the efficacy of rifaximin, a poorly absorbed antibiotic, for H. pylori eradication. Methods: We enrolled 48 consecutive H. pylori-positive patients affected. They were randomized to receive two 7-day rifaximin-based triple therapies: rifaximin tablets 400 mg t.i.d., esomeprazole 40 mg o.d. and clarithromycin 500 mg b.i.d. (CRE) or levofloxacin 500 mg o.d. (LRE). H. pylori eradication was assessed using a ¹³C-urea breath test 4 weeks after the end of therapy. Treatment compliance and the incidence of side effects were also evaluated. Results: No dropouts were observed. The eradication rate both on intention-to-treat and per-protocol analysis did not show significant differences between groups: 58% (14/24 patients) in group 1 and 42% (10/24 patients) in group 2 (p = 0.24, OR 1.96, 95% CI 0.62–6.18). No significant differences in patients’ compliance and incidence of side effects were found between groups. Conclusions: Rifaximin-based therapy showed optimal compliance but a limited eradication rate compared to standard first-line treatment. Further investigations are needed to evaluate different dosages and combinations.

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Rifaximin dose‐finding study for the treatment of small intestinal bacterial overgrowth

Cited by 108 publications

References 18 publications

Restricting Fermentative Potential by Proteome Remodeling

Restricting Fermentative Potential by Proteome Remodeling

Eradication of <i>Helicobacter pylori</i>: Are Rifaximin-Based Regimens Effective?

Rifaximin-Based Regimens for Eradication of <i>Helicobacter pylori</i>: A Pilot Study

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