Novel therapeutic strategies for Clostridium difficile infections

Expert Opin Ther Targets. 2016;20(3):269-85. doi: 10.1517/14728222.2016.1090428. Epub 2015 Nov 13.

Abstract

Introduction: In recent years, Clostridium difficile has become the primary cause of antibiotic-associated diarrhea and pseudomembranous colitis, resulting in long and complicated hospital stays that represent a serious burden for patients as well as health care systems. Currently, conservative treatment of C. difficile infection (CDI) relies on the antibiotics vancomycin, metronidazole or fidaxomicin, or in case of multiple recurrences, fecal microbiota transplantation (FMT).

Areas covered: The fast-spreading, epidemic nature of this pathogen urgently necessitates the search for alternative treatment strategies as well as antibiotic targets. Accordingly, in this review, we highlight the recent findings regarding virulence associated traits of C. difficile, evaluate their potential as alternative drug targets, and present current efforts in designing inhibitory compounds, with the aim of pointing out possibilities for future treatment strategies.

Expert opinion: Increased attention on systematic analysis of the virulence mechanisms of C. difficile has already led to the identification of several alternative drug targets. In the future, applying state of the art 'omics' and the development of novel infection models that mimic the human gut, a highly complex ecological niche, will unveil the genomic and metabolic plasticity of this pathogen and will certainly help dealing with future challenges.

Keywords: C. difficile infection; CDAD; Clostridium difficile; alternative drug targets; antibiotic resistance; small inhibitors; therapeutics; toxins; virulence factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Clostridioides difficile / drug effects*
  • Clostridioides difficile / isolation & purification
  • Clostridioides difficile / pathogenicity
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / microbiology
  • Drug Design
  • Hospitalization
  • Humans
  • Length of Stay

Substances

  • Anti-Bacterial Agents