Clostridium difficile

Written by Jaber Aslanzadeh, Ph.D.; Director of Microbiology

Clostridium difficile is a spore-forming, gram-positive bacterium that produces exotoxins that are pathogenic to humans. The main prerequisite for establishing C . difficile disease is the disruption of the normal microflora of the gut, which confer resistance to C. difficile infection, by the use of antibiotics or antineoplastic agents with antimicrobial activity. Once the antibiotic has rendered the gut more susceptible to C. difficile, infection occurs following exposure to the organism. Once colonized, C. difficile releases two potent toxins, toxin A and toxin B, which bind to certain receptors in the lining of the colon and ultimately cause diarrhea and inflammation of the large intestine. Although nearly all antibiotics have been implicated with this disease, the most common antibiotics associated with C. difficile infection are ampicillin, amoxicillin, cephalosporins, and clindamycin. C. difficile associated disease (CDAD) ranges in severity from mild diarrhea to fulminant colitis and death. It may present as a mild colitis or simple diarrhea, which develops 4 to 9 days after the beginning of antibiotic therapy. C. difficile can also cause a more serious illness with patients experiencing watery diarrhea, 10 to 20 times a day, abdominal pain, low-grade fever and dehydration. The most serious and life threatening manifestation of C. difficile infection, however, is pseudomembranous colitis. Patients with this form of the disease experience severe lower abdominal pain, diarrhea, and high fever with chills, increased heart rate and death. C. difficile typically affects older or severely ill patients who are hospitalized or are residents of a long-term-care facility. Recently, however, there has been significant increase both in the frequency and severity of CDAD⁽¹⁾. One possible explanation for this increase is the emergence of a new strain of C. difficile⁽²⁾ which produces as much as 20 times more toxin A and toxin B compared with other common strains⁽³⁾. It has a high recurrence rate, infects younger patients, leads to bloody diarrhea, and causes severe disease in populations previously at low risk, such as healthy individuals with little or no exposure to health-care settings or antimicrobial use.

Laboratory Diagnosis - The laboratory diagnosis of C. difficile infection is based on demonstration of C. difficile toxins in the stool of suspected patients. Although tissue culture toxin assay is considered the "gold standard', it only detects toxin B and requires 48 to 72 hours to complete. Over the past few years several rapid tests that take just a few hours to complete have been developed. They are usually qualitative and detect both C. difficile toxin A and toxin B. Similarly, at Clinical Laboratory Partners, we offer a monoclonal antibody based qualitative enzyme immunoassay that detects both C. difficile toxins. Our in-house validation of this test in comparison to the tissue culture toxin assay has a sensitivity and specificity of 93.3% and 93.8% respectively. Because of the excellent sensitivity and specificity of this test, we recommend limiting C. difficile testing to no more than one specimen per patient every other day⁽⁵⁾. Similarly, because an infected person may remain toxin positive for several days after they recover clinically, the test should not be used to predict a therapeutic outcome. As always, please do not hesitate to contact your CLP client service representative or me with your questions or concerns.

References:

1. McDonald CL, Banerjee S, Jernigan DB. Increasing incidence of Clostridium difficile-associated disease in U.S. acute care hospitals, 1992--2001 [Abstract]. In: Proceedings of the 14th Annual Scientific Meeting of the Society for Healthcare Epidemiology of America, Philadelphia, PA; April 17--20, 2004.
2. McDonald LC, Killgore GE, Thompson A, et al. Emergence of an epidemic, toxin gene variant strain of Clostridium difficile responsible for outbreaks in the United States between 2000 and 2004. N Engl J Med 2005 (in press).
3. Warny M, Pepin J, Fang A, et al. Increased toxins A and B production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 2005;366:1079--84
4. Pothoulakis, C. 2005. Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
5. Miller, JM. 1999. A guide to Specimen management in clinical microbiology 2nd ed. American Society of Microbiology Washington, DC.