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Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review.

Tsutsumi LS, Owusu YB, Hurdle JG, Sun D - Curr Top Med Chem (2014)

Bottom Line: Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality.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.

View Article: PubMed Central - PubMed

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. dianqing@hawaii.edu.

ABSTRACT
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.

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Chemical structures of antibiotics under clinical development for the treatment of CDI.
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Figure 2: Chemical structures of antibiotics under clinical development for the treatment of CDI.

Mentions: There are currently several new antibiotics in clinical development for the treatment of CDI (Table 2 and Fig. 2). Some of these clinical candidates have been previously reviewed by Johnson [129], Zucca et al. [115], Koo et al. [96], Sun et al. [130], Shah et al. [131], van Nispen tot Pannerden et al. [132], and Joseph et al. [133]. Here we review and highlight the chemistry, microbiology, and clinical relevance of these advanced agents for CDI.


Progress in the discovery of treatments for C. difficile infection: A clinical and medicinal chemistry review.

Tsutsumi LS, Owusu YB, Hurdle JG, Sun D - Curr Top Med Chem (2014)

Chemical structures of antibiotics under clinical development for the treatment of CDI.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921470&req=5

Figure 2: Chemical structures of antibiotics under clinical development for the treatment of CDI.
Mentions: There are currently several new antibiotics in clinical development for the treatment of CDI (Table 2 and Fig. 2). Some of these clinical candidates have been previously reviewed by Johnson [129], Zucca et al. [115], Koo et al. [96], Sun et al. [130], Shah et al. [131], van Nispen tot Pannerden et al. [132], and Joseph et al. [133]. Here we review and highlight the chemistry, microbiology, and clinical relevance of these advanced agents for CDI.

Bottom Line: Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality.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.

View Article: PubMed Central - PubMed

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. dianqing@hawaii.edu.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus