Comparative
            <i>In Vitro</i>
            Activities of LFF571 against Clostridium difficile and 630 Other Intestinal Strains of Aerobic and Anaerobic Bacteria

Citron, Diane M.; Tyrrell, Kerin L.; Merriam, C. Vreni; Goldstein, Ellie J. C.

doi:10.1128/aac.06305-11

Cited by 55 publications

(42 citation statements)

References 21 publications

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“…8, compound 3), a semisynthetic thiopeptide that is an inhibitor of bacterial translation acting via inhibition of elongation factor Tu (250). This compound possesses potent activity against C. difficile and most other Gram-positive anaerobes, displaying MIC 90 values of Յ0.25 g/ml, with the exception of bifidobacteria and lactobacilli (251). Recently a phase 1 first-in-human clinical trial investigated the safety and pharmacokinetics of single and multiple ascending oral doses of LFF571 in healthy subjects in a randomized, double-blind, placebo-controlled study (252).…”

Section: Lff571mentioning

confidence: 99%

Investigational Antimicrobial Agents of 2013

Pucci

Bush

2013

Clin Microbiol Rev

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SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting.

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Section: Lff571mentioning

confidence: 99%

Investigational Antimicrobial Agents of 2013

Pucci

Bush

2013

Clin Microbiol Rev

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“…Recently, two large doubleblind phase III trials showed that the antibiotic fidaxomicin was noninferior to vancomycin treatment regarding clinical cure rates and was associated with substantially lower rates of recurrent CDI (5)(6)(7). Several mechanisms may mediate the beneficial effects of fidaxomicin in CDI, including antimicrobial activity against C. difficile strains (8)(9)(10), which is due to inhibition of the transcription of bacterial RNA by RNA polymerases (11), and reduction of toxin A and B production by C. difficile (12).…”

mentioning

confidence: 99%

Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum

Koon

Hing

et al. 2014

Antimicrob Agents Chemother

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“…Favorably, 5FDQD is less active than fidaxomicin against the Bifidobacterium, Lactobacillus, and Actinomyces strains tested herein. Likewise, the MICs of 5FDQD against representatives of these genera are higher than the published MICs of fidaxomicin, vancomycin, metronidazole, and two clinical development candidates for CDI treatment-LFF-571 and surotomycin (39,41,58,81). Thus, the spectrum of 5FDQD appears to be narrower than those of established and developmental CDI therapeutics and should theoretically permit the regrowth of intestinal flora that protect against recurrence.…”

Section: Resultsmentioning

confidence: 84%

Novel Riboswitch-Binding Flavin Analog That Protects Mice against Clostridium difficile Infection without Inhibiting Cecal Flora

Blount

Megyola

Plummer

et al. 2015

Antimicrob Agents Chemother

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Despite nearly 85 years of successful antibacterial chemotherapy, bacterial infections still pose a serious threat to human health. Continually emerging drug-resistant bacteria make existing agents less effective, and a paucity of new agents and decreased development effort from the pharmaceutical industry provide little hope of replenishing the arsenal (1, 2). Complications and mortality due to bacterial infections continue to increase, already reaching epidemic proportions in some areas of the world. If humans are to regain the upper hand in fighting bacterial infections, then innovation, investment, and new antibacterial agents will be needed. Although some of the barriers to the discovery and approval of new compounds are economic or policy related, there is also a desperate need for new targets and new mechanisms of action. A renewed effort to expand our knowledge of bacterial physiology and to translate discoveries into the clinic will be needed to address these challenges and to reinvigorate antibiotic development pipelines.Recent advances in our understanding of how bacteria maintain physiological homeostasis revealed a promising class of potential antibiotic targets called riboswitches-noncoding mRNAs that form a structured receptor (or aptamer) which can directly bind to a specific small-molecule ligand or ion and thereby regulate gene expression (3-5). Ligand binding to a riboswitch aptamer stabilizes a conformationally distinct architecture in the mRNA that modulates the expression of the adjacent coding region(s) (4-8). To date, more than 35 riboswitch classes have been discovered and characterized (7). Three of these riboswitch classes have been revealed as important cellular targets of antibacterial small molecules whose mechanism of action had not been previously defined (9-13). More recently, several publications have demonstrated that novel small molecules that bind to selected riboswitch aptamers with affinities comparable to that of the cognate ligand can be rationally identified and optimized (14-21).In some cases, synthetic or natural riboswitch ligand analogs have demonstrated potent antibacterial activity (12-15, 20, 22). For example, the phosphorylated form of roseoflavin (RoF) (

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Comparative In Vitro Activities of LFF571 against Clostridium difficile and 630 Other Intestinal Strains of Aerobic and Anaerobic Bacteria

Cited by 55 publications

References 21 publications

Investigational Antimicrobial Agents of 2013

Investigational Antimicrobial Agents of 2013

Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum

Novel Riboswitch-Binding Flavin Analog That Protects Mice against Clostridium difficile Infection without Inhibiting Cecal Flora

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