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.
authors.affiliation: †The Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Angie M
authors.initials: AM
authors.lastname: Jarrad
authors.affiliation: †The Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Tomislav
authors.initials: T
authors.lastname: Karoli
authors.affiliation: †The Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Mark A T
authors.initials: MA
authors.lastname: Blaskovich
authors.affiliation: ‡School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Dena
authors.initials: D
authors.lastname: Lyras
authors.affiliation: †The Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000187:drug effects*; D055808:Drug Discovery; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents