What is Clostridium difficile?
Clostridium difficile is a Gram-positive, spore-forming bacterium. It is an opportunistic pathogen, infecting the colon of patients following antibiotic treatment. C. difficile produces two toxins, TcdA and TcdB, which damage intestinal cells and cause inflammation in the gut.
How is C. difficile infection related to antibiotic use?
The communities of microbes that normally live in the gut, called the microbiota or microbiome, usually prevent C. difficile colonization and suppress C. difficile-associated disease. Antibiotic treatment can alter the microbiota in such a way that allows C. difficile, a bacterium that is naturally resistant to many common antibiotics, to grow and cause inflammation in the colon.
What is the public health concern?
C. difficile is a major healthcare-associated infection in the United States, causing mild to severe diarrhea. According to the Centers for Disease Control and Prevention (CDC), around half a million people are infected each year, resulting in approximately 15,000 deaths. Reducing C. difficile infections is a national priority, as outlined in the National Action Plan for Combating Antibiotic-Resistant Bacteria, a comprehensive plan issued by the White House in 2015 detailing the role of Federal agencies in combatting antibiotic resistance.
How is it spread?
C. difficile is spread by the fecal-oral route. C. difficile is shed in the feces of infected patients, and its spores can survive for an extended time on surfaces. Infection can be spread by touching contaminated surfaces and ingesting spores. C. difficile spores are difficult to eliminate and are not destroyed by alcohol-based hand sanitizers.
What are the issues with treating C. difficile infection?
While susceptibility to C. difficile infection is associated with antibiotic use, the current therapies to treat the infection are also, paradoxically, antibiotics. With current treatments, approximately 20% of patients have recurrent infection. Hypervirulent strains of C. difficile have emerged in recent years, impacting the incidence and severity of infection.
What new antibiotic treatments is NIAID supporting?
Two examples of novel antimicrobials supported by NIAID include:
- CRS3123 – inhibits an enzyme required by C. difficile to make proteins. The safety and pharmacokinetics of CRS3123 are being evaluated in a Phase I trial, conducted through the NIAID-supported Phase I Clinical Trial Units.
- Amixicile – targets an enzyme found in anaerobic bacteria, like C. difficile, but is absent in beneficial probiotic bacteria. NIAID is supporting the preclinical development of Amixicile.
Is NIAID supporting the development of non-antibiotic treatments?
NIAID-supported scientists are researching how changes in the gut microbiota can allow C. difficile colonization. These data may inform the development of novel microbiota-based therapeutics. NIAID-supported scientists found that certain metabolites become more abundant in the gut after antibiotic use, increasing susceptibility to C. difficile infection. Researchers supported by NIAID also found that susceptibility to C. difficile infection was related to distinct changes in the gut microbiota and identified bacteria that can restore resistance to C. difficile colonization.
What vaccine research is NIAID supporting?
NIAID is supporting preclinical research to develop new vaccine targets and strategies for C. difficile. Some examples include:
- The development of potential vaccine which targets the C. difficile toxins.
- The use of bacterial adherence factors as potential subunit vaccine candidates.
- The development of live vector vaccines against C. difficile.
What basic research is being done to better understand C. difficile infection?
The NIAID Structural Genomics Centers have generated more than 220 structures of proteins from pathogen species and genera associated with antimicrobial resistance, including C. difficile. NIAID-supported research is focused on understanding basic mechanisms of C. difficile spore-formation and spore germination. NIAID is supporting clinical research studies looking at C. difficile fitness and spread within health care facilities.
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