Clostridium difficile drug pipeline: challenges in discovery and development of new agents

Angie M Jarrad, Tomislav Karoli, Mark A T Blaskovich, Dena Lyras, Matthew A Cooper

Research output: Contribution to journal › Article › Research › peer-review

Abstract

In the past decade Clostridium difficile has become a bacterial pathogen of global significance. Epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. In response to the increasing medical burden, a new C. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of C. difficile-associated diarrhea. Rudimentary fecal transplants are also being trialed as effective treatments. Despite these advances, therapies that are more effective against C. difficile spores and less damaging to the resident gastrointestinal microbiome and that reduce recurrent disease are still desperately needed. However, bringing a new treatment for C. difficile infection to market involves particular challenges. This review covers the current drug discovery pipeline, including both small molecule and biologic therapies, and highlights the challenges associated with in vitro and in vivo models of C. difficile infection for drug screening and lead optimization.
Original languageEnglish
Pages (from-to)5164 - 5185
Number of pages22
JournalJournal of Medicinal Chemistry
Volume58
Issue number13
DOIs
Publication statusPublished - 2015

Cite this

Jarrad, Angie M ; Karoli, Tomislav ; Blaskovich, Mark A T ; Lyras, Dena ; Cooper, Matthew A. / Clostridium difficile drug pipeline: challenges in discovery and development of new agents. In: Journal of Medicinal Chemistry. 2015 ; Vol. 58, No. 13. pp. 5164 - 5185.
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title = "Clostridium difficile drug pipeline: challenges in discovery and development of new agents",
abstract = "In the past decade Clostridium difficile has become a bacterial pathogen of global significance. Epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. In response to the increasing medical burden, a new C. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of C. difficile-associated diarrhea. Rudimentary fecal transplants are also being trialed as effective treatments. Despite these advances, therapies that are more effective against C. difficile spores and less damaging to the resident gastrointestinal microbiome and that reduce recurrent disease are still desperately needed. However, bringing a new treatment for C. difficile infection to market involves particular challenges. This review covers the current drug discovery pipeline, including both small molecule and biologic therapies, and highlights the challenges associated with in vitro and in vivo models of C. difficile infection for drug screening and lead optimization.",
author = "Jarrad, {Angie M} and Tomislav Karoli and Blaskovich, {Mark A T} and Dena Lyras and Cooper, {Matthew A}",
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publisher = "AMER CHEMICAL SOC",
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Jarrad, AM, Karoli, T, Blaskovich, MAT, Lyras, D & Cooper, MA 2015, 'Clostridium difficile drug pipeline: challenges in discovery and development of new agents' Journal of Medicinal Chemistry, vol. 58, no. 13, pp. 5164 - 5185. https://doi.org/10.1021/jm5016846

Clostridium difficile drug pipeline: challenges in discovery and development of new agents. / Jarrad, Angie M; Karoli, Tomislav; Blaskovich, Mark A T; Lyras, Dena; Cooper, Matthew A.

In: Journal of Medicinal Chemistry, Vol. 58, No. 13, 2015, p. 5164 - 5185.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Clostridium difficile drug pipeline: challenges in discovery and development of new agents

AU - Jarrad, Angie M

AU - Karoli, Tomislav

AU - Blaskovich, Mark A T

AU - Lyras, Dena

AU - Cooper, Matthew A

PY - 2015

Y1 - 2015

N2 - In the past decade Clostridium difficile has become a bacterial pathogen of global significance. Epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. In response to the increasing medical burden, a new C. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of C. difficile-associated diarrhea. Rudimentary fecal transplants are also being trialed as effective treatments. Despite these advances, therapies that are more effective against C. difficile spores and less damaging to the resident gastrointestinal microbiome and that reduce recurrent disease are still desperately needed. However, bringing a new treatment for C. difficile infection to market involves particular challenges. This review covers the current drug discovery pipeline, including both small molecule and biologic therapies, and highlights the challenges associated with in vitro and in vivo models of C. difficile infection for drug screening and lead optimization.

AB - In the past decade Clostridium difficile has become a bacterial pathogen of global significance. Epidemic strains have spread throughout hospitals, while community acquired infections and other sources ensure a constant inoculation of spores into hospitals. In response to the increasing medical burden, a new C. difficile antibiotic, fidaxomicin, was approved in 2011 for the treatment of C. difficile-associated diarrhea. Rudimentary fecal transplants are also being trialed as effective treatments. Despite these advances, therapies that are more effective against C. difficile spores and less damaging to the resident gastrointestinal microbiome and that reduce recurrent disease are still desperately needed. However, bringing a new treatment for C. difficile infection to market involves particular challenges. This review covers the current drug discovery pipeline, including both small molecule and biologic therapies, and highlights the challenges associated with in vitro and in vivo models of C. difficile infection for drug screening and lead optimization.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500462/pdf/jm5016846.pdf

U2 - 10.1021/jm5016846

DO - 10.1021/jm5016846

M3 - Article

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EP - 5185

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 13

ER -

Jarrad AM, Karoli T, Blaskovich MAT, Lyras D, Cooper MA. Clostridium difficile drug pipeline: challenges in discovery and development of new agents. Journal of Medicinal Chemistry. 2015;58(13):5164 - 5185. https://doi.org/10.1021/jm5016846

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