The challenge of Clostridium difficile-associated diarrhea (CDAD)

C. difficile is a spore-forming, gram-positive anaerobe1

  • C. difficile produces two toxins, A and B, which activate the release of cytokines from monocytes2

  • Toxins A and B lead to inflammation, intestinal epithelial cell damage, fluid secretion, and diarrhea, as well as other symptoms3

Transmission of C. difficile4

  • The primary mode of transmission is person-to-person spread through the fecal-oral route

  • Environmental contamination also plays an important role (eg, commodes, bedpans, thermometers, etc)

Pathogenesis of C. difficile3,5

  • C. difficile-ingested spores are able to survive the acidic stomach
  • Spores reach the small intestine and germinate to vegetative form
  • If intestinal microflora is disrupted, C. difficile can proliferate
  • Toxigenic strains of C. difficile may produce clinical disease

 

Petri dish

 

C. difficile: a persistent pathogen

  • C. difficile spores can be stable for months and cultured from hospital surfaces (eg, railings, bedpans, walls, floors, sinks, etc)4
    • Spores are resistant to antibacterial soaps, alcohol-based hand sanitizers, and conventional disinfectants4
  • The vegetative form of C. difficile can survive in the environment on moist surfaces for up to 6 hours5
    • Vegetative form is susceptible to gastric acid, antibacterial soaps, and alcohol-based hand sanitizers6
  • Formation of spores and the inadequacy of standard methods of disinfection (not killed by conventional detergents or solvents) lead to persistence in the environment and the spread of infection4
  • Disinfection requires bleach or other strong oxidizers (eg, peroxide), extreme heat (greater than the boiling point of water), or long contact times7
    • CDC recommends meticulous cleaning followed by use of hypochlorite-based germicides for desinfection of surfaces in patient-care areas7

 

Important Safety Information

  • DIFICID is contraindicated in patients with hypersensitivity to fidaxomicin
  • DIFICID should not be used for systemic infections
  • Acute hypersensitivity reactions (angioedema, dyspnea, pruritus, and rash) have been reported. In the event of a severe reaction, discontinue DIFICID.
  • Only use DIFICID for infection proven or strongly suspected to be caused by C. difficile.
    Prescribing DIFICID in the absence of a proven or strongly suspected C. difficile infection is unlikely to provide benefit to the patient and increases the risk of the development of drug- resistant bacteria.
  • The most common adverse reactions reported in clinical trials are nausea (11%), vomiting (7%), abdominal pain (6%), gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%)

 

Indications and Usage

  • DIFICID is a macrolide antibacterial drug indicated in adults ≥18 years of age for treatment of Clostridium difficile-associated diarrhea
  • To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by Clostridium difficile

 

Please click here for full prescribing information for DIFICID.


1. McDonald LC, Killgore GE, Thompson A, et al. An epidemic, toxin gene-variant strain of Clostridium difficile. N Engl J Med. 2005;353(23):2433-2441.

 
2. Flegel WA, Müller F, Däubener W, Fischer HG, Hadding U, Northoff H. Cytokine response by human monocytes to Clostridium difficile toxin A and toxin B. Infect Immun. 1991;59(10):3659-3666.
 
3. Sunenshine RH, McDonald LC. Clostridium difficile–associated disease: new challenges from an established pathogen. Cleve Clin J Med. 2006;73(2):187-197.
 
4. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431-455.
 
5. Jump RLP, Pultz MJ, Donskey CJ. Vegetative Clostridium difficile survives in room air on moist surfaces and in gastric contents with reduced acidity: a potential mechanism to explain the association between proton pump inhibitors and C. difficile-associated diarrhea? Antimicrob Agents Chemother. 2007;51(8):2883-2887.
 
6. Fordtran JS. Colitis due to Clostridium difficile toxins: underdiagnosed, highly virulent, and nosocomial. Proc (Bayl Univ Med Cent). 2006;19(1):3-12.
 
7. Gould C, McDonald C; for the Centers for Disease Control and Prevention. Clostridium difficile (CDI) infections toolkit. http://www.cdc.gov/HAI/pdfs/toolkits/CDItoolkitwhite_clearance_edits.pdf. Published December 23, 2009. Accessed May 21, 2011.