Evaluation of NVB302 versus vancomycin activity in an in vitro human gut model of Clostridium difficile infection

Crowther, Grace S.; Baines, Simon D.; Todhunter, Sharie L.; Freeman, Joseph T.; Chilton, Caroline H.; Wilcox, Mark H.

doi:10.1093/jac/dks359

Cited by 104 publications

(57 citation statements)

References 28 publications

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“…It is highly selective for C. difficile versus normal gut flora, which may diminish the chance for recurrent infections. NVB302 displayed noninferiority to vancomycin in the treatment of simulated C. difficile infection in an in vitro human gut model (253). Novacta recently completed a phase 1 clinical trial in healthy volunteers, and NVB302 was found to be safe and well tolerated, with negligible systemic absorption of the drug and high concentrations recovered in the feces.…”

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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“…Some promising candidates have been undergoing preclinical trials, like mutacin 1140 (MU1140) for dental and oral care, microbisporicin (NAI-107) for controlling severe infections caused by multidrugresistant Gram-positive pathogens, and lacticin 3147 for the treat-ment of systemic S. aureus infections (10)(11)(12). In addition, NVB302 (an actagardine derivative) and Moli1901 (duramycin) have completed phase I and phase II clinical trials for the treatment of Clostridium difficile infections (13) and cystic fibrosis (14,15). Hence, exploring novel and potent lantibiotics for clinical application has become a major interest with a promising future.…”

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confidence: 99%

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Wang

Zhang

Teng

et al. 2014

Appl Environ Microbiol

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Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of the Bacillus group. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled in Bacillus cereus strain As 1.1846 through genomic mining and PCR screening. The designated cer locus is different from that of conventional class II lantibiotics in that it included seven tandem precursor cerA genes, one modification gene (cerM), two processing genes (cerT and cerP), one orphan regulator gene (cerR), and two immunity genes (cerF and cerE). In addition, one unprecedented quorum sensing component, comQXPA, was inserted between cerM and cerR. The expression of cerecidins was not detected in this strain of B. cereus, which might be due to repressed transcription of cerM. We constitutively coexpressed cerA genes and cerM in Escherichia coli, and purified precerecidins were proteolytically processed with the endoproteinase GluC and a truncated version of putative serine protease CerP. Thus, two natural variants of cerecidins A1 and A7 were obtained which contained two terminal nonoverlapping thioether rings rarely found in lantibiotics. Both cerecidins A1 and A7 were active against a broad spectrum of Gram-positive bacteria. Cerecidin A7, especially its mutant Dhb13A, showed remarkable efficacy against multidrug-resistant Staphylococcus aureus (MDRSA), vancomycin-resistant Enterococcus faecalis (VRE), and even Streptomyces.

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“…Crowther et al conducted a recent study investigating the efficacy of NVB302 compared to vancomycin in treating CDI employing an in vitro gut model. 86 The gut microbiota count as well as C. difficile viable counts and spores were enumerated following NVB302 and vancomycin administration and a decrease in viable C. difficile counts with vancomycin and NVB302 administration was noted. NVB302 performed better than vancomycin as cytotoxin levels were undetectable 7 d subsequent to NVB302 administration, compared to undetectable cytotoxin levels 5 d after vancomycin instillation.…”

Section: Actagardine and Nvb302mentioning

confidence: 99%