An 81-year-old man is hospitalized with a history of fevers (38.6 C) for the preceding five days. Because of confusion and inability to care for himself, he has resided in a local nursing home for the past three years. However, he had been able to dress himself and move about the wards until a week before his hospital admission, when he complained of weakness and could not get out of bed. He had not experienced any recent illness, except for a urinary tract infection that occurred four weeks ago, for which he was treated with a ten-day course of ampicillin.

On physical examination, the patient is resting comfortably in bed but appears confused and rather unhappy about his change of surroundings. His temperature is 39 C, but his other vital signs are normal. There are no localized physical findings and the abdominal examination is unremarkable.

The next morning, the house staff and attending physician are pondering diagnostic possibilities at the patient's bedside when a nurse informs them that the patient passed two loose bowel movements during the night. Indeed, the attending physician's olfaction, perhaps heightened by the new information, now recognizes the occurrence of another such event, most likely triggered by deep palpation of the patient's abdomen. The attending physician calls the patient's nursing home and learns that none of the other residents have reported symptoms like those experienced by this patient.

Question 4.1: What is your preliminary diagnosis?

The current symptoms are consistent with some type of acute gastroenteritis. The fever implies an inflammatory form of gastroenteritis. Commonly occurring examples include salmonellosis, shigellosis (bacterial dysentery), Campylobacter gastroenteritis, enterohemorrhagic Escherichia coli (EHEC) gastroenteritis, and several other afflictions. Many of these diseases are often associated with a common source of infection, such as contaminated food or water. That route of infection seems unlikely in this case, however, since none of the other nursing home residents are ill. Because there is no evidence of a food- or water-borne illness and because the patient has a history of recent antibiotic treatment, one should consider Clostridium difficile gastroenteritis as the most likely diagnosis in this situation. ºC. difficile is the most frequent cause of gastroenteritis in patients who are taking antibiotics or who have taken them in recent days to weeks.)

Question 4.2: What tests should you do?

A stool specimen should be examined for blood and inflammatory cells. A stool culture should be done and you should ask the lab to test specifically for C. difficile enterotoxin in the stool.

Test Results

The lab reports that erythrocytes and fecal polymorphonuclear leukocytes are present in this patient's stool. The stool culture is negative for common GI pathogens like Salmonella or Shigella. However, the test for C. difficile toxin is positive.

Question 4.3: Where did the causative agent come from?

Clostridium difficile is harbored in the large intestine of humans, where it tends remain in a dormant state in relatively low numbers. It can also be found in environmental sources, particularly hospitals. Under adverse conditions, the organism reverts to its highly resistant spore form. The spores can be cultured from the floor, bedpan, and toilet in a hospital room occupied by a patient with an active C. difficile infection, as well as from the hands and clothing of medical and nursing personnel. The mode of transmission is via the spore form, which can be extremely difficult to eradicate from the local environment. C. difficile is the major cause of diarrhea acquired during treatment in a hospital. In nursing homes, where patients tend to stay for prolonged periods, 20-30% of the residents are asymptomatic carriers of C. difficile. In the present case, the patient most likely acquired the organism at his nursing home and was an asymptomatic carrier of it.

Question 4.4: What was the role of antibiotics in this case?

C. difficile diarrhea is closely linked to the use of antimicrobial drugs; most symptomatic patients have taken an antimicrobial agent in the recent past. Virtually all antimicrobial drugs have been implicated, but those most closely associated with C. difficile diarrhea are cephalosporins, ampicillin, and clindamycin. These drugs suppress or kill most members of the normal bacterial flora in the intestine, but they are ineffective against the spore form of C. difficile. C. difficile is either already present in the flora (as in the present case) or is acquired from the hospital environment during antibiotic treatment. The bacterium enters the spore state in response to the threat posed by the antibiotic and, thereby, remains resistant to the drug. At some time during or after antibiotic administration, the spores germinate and vegetative form of C. difficile grows extensively because the normal bacterial flora of the intestine that would normally out-compete it for nutrients and other resources has not yet been restored.

Question 4.5: How does this causative agent produce disease?

When allowed to grow extensively in the intestine (usually after antibiotic treatment), C. dfficile produces toxins in the intestinal lumen, and these toxins cause damage to the epithelial lining of the bowel wall. (The organism does not invade the epithelial surface of bowel wall.) The major toxins are designated A and B. Toxin A causes both fluid production and damage to the mucosa of the large bowel, and it is responsible for the clinical disease. Toxin B is a cytotoxin that produces abnormalities in tissue-culture systems. The standard laboratory test that diagnoses C. difficile diarrhea uses this property to detect the toxin.

Question 4.6: How can this case be treated?

Metronidazole is a possibility, although some patients relapse or won't tolerate it. Vancomycin is generally more effective, but far more expensive. The recommended regimen would be 125 mg PO qid.