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Discovery and development of surotomycin for the treatment of Clostridium difficile

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Journal of Industrial Microbiology & Biotechnology

Abstract

The primary challenge for treating Clostridium difficile infections (CDI) is maintenance of clinical response after the end of treatment (sustained clinical response). Disease recurrence following a positive clinical response occurs in approximately 6–25 % of patients after the first episode and in up to 65 % for subsequent recurrences. Surotomycin, a novel cyclic lipopeptide antibiotic with a core derived by Streptomyces roseosporus fermentation, disrupts C. difficile cellular membrane activity in both logarithmic and stationary phases and minimally disturbs normal gastrointestinal microbiota because of its lack of activity against Gram-negative anaerobes and facultative anaerobes. Preclinical and clinical evidence indicate that surotomycin has low oral bioavailability, allowing gastrointestinal tract concentrations to greatly exceed its minimum inhibitory concentration for C. difficile. Surotomycin is well tolerated and effective in hamster models of CDI. Phase 2 clinical evidence suggests that surotomycin (250 mg twice daily) is an effective CDI treatment, with statistically lower recurrence rates than vancomycin.

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Acknowledgments

Financial support for medical editorial assistance was provided by Cubist Pharmaceuticals. We thank Tamalette Loh, PhD, ProEd Communications, Inc., for her medical editorial assistance with this manuscript.

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  1. Laurent Chesnel

    Present address: Merck & Co., Inc., Lexington, MA, USA

Authors and Affiliations

  1. Cubist Pharmaceuticals, Lexington, MA, USA

    Victoria Knight-Connoni, Carmela Mascio, Laurent Chesnel & Jared Silverman

  2. Clinical Microbiology, Merck Research Labs, 65 Hayden Avenue, Lexington, MA, 02421, USA

    Laurent Chesnel

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  1. Victoria Knight-Connoni
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  2. Carmela Mascio
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Correspondence to Laurent Chesnel.

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Conflict of interest

Victoria Knight-Connoni reports that work performed on this publication was done while employed by Cubist Pharmaceuticals. Carmela Mascio reports that work performed on this publication was done while employed by Cubist Pharmaceuticals. Laurent Chesnel reports that work performed on this publication was done while employed by Cubist Pharmaceuticals, and current employment and stock ownership from Merck. Jared Silverman reports that he was an employee of Cubist Pharmaceuticals during the research and manuscript preparation.

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Special Issue: Natural Product Discovery and Development in the Genomic Era. Dedicated to Professor Satoshi Ōmura for his numerous contributions to the field of natural products.

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Knight-Connoni, V., Mascio, C., Chesnel, L. et al. Discovery and development of surotomycin for the treatment of Clostridium difficile . J Ind Microbiol Biotechnol 43, 195–204 (2016). https://doi.org/10.1007/s10295-015-1714-6

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  • DOI: https://doi.org/10.1007/s10295-015-1714-6

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