Pseudomembranous Clostridium Difficile Colitis

Introduction

Clostridium difficile was originally described as a component of the normal intestinal flora of newborn infants by Hall and O’Toole in 1935, who also demonstrated that this organism produced a toxin extremely lethal to mice. However, the “ C. difficile era” began in 1974 when Tedesco et al reported high rates of pseudomembranous colitis in patients exposed to clindamycin at Barnes Hospital in St. Louis, Mo. Furthermore, this study was the first to use endoscopy as a diagnostic tool for patients with antibiotic-associated diarrhea.

C. difficile –associated diarrhea (CDAD) is presently the most common form of nosocomial diarrhea in the United States. According to the Centers for Disease Control and Prevention, the annual incidence of C. difficile infection (CDI) exceeds 250,000 hospitalized cases, and the prevalence measured by the National Hospital Discharge Survey is estimated to be 9.4 cases per 1000 discharges with a mortality rate of 1% to 2.5%. On the basis of current incidence rates, annual costs for management of CDI range between $800 million and $3.2 billion in the United States per year. Although CDI primarily is considered to be a nosocomial infection, recent population and hospital-based studies have reported an epidemiologic shift during the previous decade, including an increased incidence among outpatient cohorts as well as hospitalized patients. Furthermore, new studies discovered that these changes in the epidemiology were connected with the development of hypervirulent strains of C. difficile , currently recognized as NAP1/BI/027 strains.

C. difficile, a spore-forming gram-positive bacterium, is a normal component of gastrointestinal flora in up to 3% of healthy adults and is present in up to 20% of persons who are receiving antibiotic treatment. In several studies, the period between exposure to C. difficile and the occurrence of CDI has been estimated to be a median of 2 to 3 days. The primary mode of C. difficile transmission resulting in disease is person-to-person spread through the fecal-oral route, principally within inpatient health care facilities. C. difficile spores are resistant to gastric acidity and are able to evolve into the vegetative form in the small intestine after ingestion. Colonization of the colon then occurs after the normal flora is disrupted by the use of antibiotics or other predisposing host factors. Once the colonization is accomplished, the bacteria produces exotoxins and other virulence factors that are toxic to colonic mucosa and initiate local and systemic inflammatory cascades. Clinical presentation ranges from asymptomatic infection or diarrhea when the injury is limited to the colonic mucosa to severe fulminant colitis when the consequences of the toxemia become systemic.

Major risk factors for the development of CDAD are advanced age (>65 years), prior hospitalization, and use of antibiotics. Certain antibiotics have been associated with nosocomial CDI, such as clindamycin, second- and third-generation cephalosporins (especially ceftriaxone), and fluoroquinolones. When subdividing antibiotics for outpatient cohorts, the use of phenoxymethylpenicillin, dicloxacillin, and penicillins with extended spectra remained statistically significant in a multivariable model analysis as a risk factor for the development of CDAD. However, neither the antibiotic dosage nor the length of administration has been found to correlate with the development of CDI. Other risk factors associated with CDAD include admissions to long-term care facilities, immunosuppression, postoperative state, use of proton pump inhibitors, elemental diets, inflammatory bowel disease, and chemotherapy.

Presentation of Clostridium Difficile Infection

The severity of symptoms of CDI is highly variable, ranging from diarrhea to life-threatening colitis and systemic toxemia. The severity of the disease is likely determined by host factors in combination with the virulence of the toxin produced by the infecting strain. Typical features include watery diarrhea, with as many as 15 to 30 bowel movements per day, and leukocytosis. Many patients report abdominal pain or cramps (30% to 60%) and fever (28%). Some patients do not present with diarrhea and instead demonstrate an ileus.

The peripheral leukocyte count is usually 10,000 to 20,000 leukocytes/mm ³ but may approach 50,000 leukocytes/mm ³ . Hypoalbuminemia is a common feature over time because CDI is a protein-losing enteropathy, and patients who are already malnourished for other reasons may be at higher risk of contracting CDI. In rare circumstances, patients experience ileus, toxic megacolon, and colonic perforation.