Clostridium difficile infection (CDI) is a unique colonic disease that is acquired almost exclusively in association with antimicrobial use and the consequent disruption of the normal colonic flora. The most commonly diagnosed diarrheal illness acquired in the hospital, CDI results from the ingestion of spores of C. difficile that vegetate, multiply, and secrete toxins, causing diarrhea and pseudomembranous colitis (PMC).
Etiology and Epidemiology
C. difficile is an obligately anaerobic, gram-positive, spore-forming bacillus whose spores are found widely in nature, particularly in the environment of hospitals and chronic-care facilities. CDI occurs most frequently in hospitals and nursing homes where the level of antimicrobial use is high and the environment is contaminated by C. difficile spores.
Clindamycin, ampicillin, and cephalosporins were the first antibiotics associated with CDI. The second- and third-generation cephalosporins, particularly cefotaxime, ceftriaxone, cefuroxime, and ceftazidime, are agents frequently responsible for this condition, and the fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin) are the most recent drug class to be implicated in hospital outbreaks. Penicillin/β-lactamase-inhibitor combinations such as ticarcillin/clavulanate and piperacillin/tazobactam pose significantly less risk. However, all antibiotics, including vancomycin and metronidazole (the agents most commonly used to treat CDI), have been found to carry a risk of subsequent CDI. Rare cases are reported in patients without prior antibiotic exposure.
C. difficile is acquired exogenously, most frequently in the hospital or nursing home, and is carried in the stool of symptomatic and asymptomatic patients. The rate of fecal colonization is often ≥20% among adult patients hospitalized for >1 week; in contrast, the rate is 1–3% among community residents. Community-onset CDI without recent hospitalization probably accounts for ≤10% of all cases. The risk of C. difficile acquisition increases in proportion to length of hospital stay. Asymptomatic fecal carriage of C. difficile in healthy neonates is very common, with rates often exceeding 50% during the first 6 months of life, but associated disease in this population is rare. Spores of C. difficile are found on environmental surfaces (where the organism can persist for months) and on the hands of hospital personnel who fail to practice good hand hygiene. Hospital epidemics of CDI have been attributed to a single C. difficile strain and to multiple strains present simultaneously. Other identified risk factors for CDI include older age, greater severity of underlying illness, gastrointestinal surgery, use of electronic rectal thermometers, enteral tube feeding, and antacid treatment. Use of proton pump inhibitors may be a risk factor, but this risk is probably modest, and no firm data have implicated these agents in patients who are not already receiving antibiotics.
Pathology and Pathogenesis
Spores of toxigenic C. difficile are ingested, survive gastric acidity, germinate in the small bowel, and colonize the lower intestinal tract, where they elaborate two large toxins: toxin A (an enterotoxin) and toxin B (a cytotoxin). These toxins initiate processes resulting in the disruption of epithelial-cell ...