Clostridium difficile infection (CDI) is a unique colonic disease that is acquired most often in association with antimicrobial use and the consequent disruption of the normal colonic microbiota. 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) in the most severe cases.
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 frequently in hospitals and nursing homes (or shortly after discharge from these facilities) 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 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), 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, but also possibly in the outpatient setting—and is carried in the stool of both 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, nursing home residence, or outpatient health-care contact probably accounts for ≤10% of all cases. The risk of C. difficile acquisition increases in proportion to the length of hospital stay. Asymptomatic fecal carriage of C. difficile in healthy neonates is very common, with repeated colonization by multiple strains in infants (<1 year old), but associated disease in these infants is extremely rare if it occurs at all. 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 ...