Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review
Lissa S. Tsutsumi, Yaw B. Owusu, Julian G. Hurdle and Dianqing Sun
Affiliation: Department of Pharmaceutical Sciences, The Daniel K. Inouye College of Pharmacy, University of Hawai’i at Hilo, 34 Rainbow Drive, Hilo, HI 96720, USA.
Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in
significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly
high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics,
and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection
have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently
needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical
treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported
anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug
discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds
that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity,
reduced cytotoxicity, and novel modes of action to prevent resistance.
Keywords: Antibiotics, clinical, Clostridium difficile, Clostridium difficile infection, natural products, small molecules, treatment.
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