Clostridium Difficile - Cause

Cause

With the introduction of broad-spectrum antibiotics and chemotherapeutic antineoplastic drugs in the second half of the 20th century, antibiotic- and chemotherapy-associated diarrhea became more common. Pseudomembranous colitis was first described as a complication of C. difficile infection in 1978, when a toxin was isolated from patients suffering from pseudomembranous colitis and Koch's postulates were met.

The many spores formed by C. difficile are resistant to most routine cleaning methods used on surfaces (except for diluted bleach). Spores of these bacteria can remain viable outside of the human body for very long periods of time, and this means the patients in a medical facility are often exposed to situations where they end up accidentally ingesting spores. Extremely rigorous infection protocols are required to decrease or eliminate this risk.

C. difficile infection (CDI) can range in severity from asymptomatic to severe and life-threatening, especially among the elderly. People are most often nosocomially infected in hospitals, nursing homes, or other medical institutions, although CDI in the community, outpatient setting is increasing. The rate of C. difficile acquisition is estimated to be 13% in patients with hospital stays of up to two weeks, and 50% in those with hospital stays longer than four weeks. C. difficile-associated diarrhea (CDAD) is most strongly associated with fluoroquinolones, cephalosporins, carbapenems, and clindamycin. In addition to previous use of antimicrobials, use of proton pump inhibitors is associated with a two-fold increase in risk for CDI.

The European Center for Disease Prevention and Control recommend the fluoroquinolones and the antibiotic clindamycin be avoided in clinical practice due to their high association with subsequent CDIs. Frequency and severity of C. difficile colitis remains high and seems to be associated with increased death rates. Immunocompromised status and delayed diagnosis appear to result in elevated risk of death. Early intervention and aggressive management are key factors to recovery.

Increasing rates of community-acquired CDI are associated with the use of medication to suppress gastric acid production: H2-receptor antagonists increased the risk 1.5-fold, and proton pump inhibitors by 1.7 with once-daily use and 2.4 with more than once-daily use.

The emergence of a new, highly toxic strain of C. difficile, resistant to fluoroquinolone antibiotics, such as ciprofloxacin (Cipro) and levofloxacin (Levaquin), is said to be causing geographically dispersed outbreaks in North America was reported in 2005. The Centers for Disease Control in Atlanta has also warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both.

In 2005, molecular analysis led to the identification of the C. difficile strain type characterized as group BI by restriction endonuclease analysis (REA), as North American pulse-field-type NAP1 by pulse-field gel electrophoresis (PFGE) and as ribotype 027; the differing terminology reflects the predominant techniques that were used for epidemiological typing, and this strain is referred to as C. difficile BI/NAP1/027.

Some recent research suggests the overuse of antibiotics in the raising of livestock for meat consumption is contributing to outbreaks of bacterial infections such as C. difficile.