only 3% of healthy adults are colonized. Colonization increases to 20% to 30% of hospitalized
adults (26), but clinical symptoms develop in only one-third of those who become colonized
(34). The immune response of the host plays a role in determining who becomes an
asymptomatic carrier and who develops CDI. Colonization has been shown to decrease the
risk of developing CDI. However, colonized individuals shed pathogenic organisms and serve
as a reservoir for environmental contamination.
CDI ranges over a wide spectrum of disease, and there are no pathognomonic findings
on history or physical exam. The definition of CDI includes >3 unformed stools over 24 hours
for at least 2 days and either a positive stool test for the presence of toxigenicC. difficileor
C. difficiletoxins or a colonoscopy revealing pseudomembranes (Table 2). To date, there is no
prospective scoring system for CDI severity that has been validated. The important
classification of CDI into mild, moderate, and severe disease is therefore based on criteria
that may differ between studies.
The most common clinical presentation of CDI in the hospital is diarrhea associated with
a history of antibiotic use. Symptoms can begin as early as the first day of antibiotic use or as
late as eight weeks after completion of the precipitating antibiotic course (25). Most commonly,
symptoms develop within four to nine days (3).
- For mild disease, the diarrhea is usually the only symptom, involving<10 episodes a
day without systemic symptoms. The diarrhea is frequently watery with a
characteristic foul odor, but it can also be mucoid or mushy. It is rarely bloody. - Moderate disease, defined as <10 bowel movements per day, leukocytosis
<15,000 cells/mL, and creatinine<1.5 times premorbid level, may result in profuse
diarrhea, abdominal distention, or abdominal pain located in the lower quadrants, fever,
tachycardia, and oliguria, which usually responds readily to volume resuscitation. - Severe disease defined as >10 bowel movements per day, leukocytosis
15,000 cells/mL, elevated creatinine (>1.5 times premorbid level), fever
(which may be absent in an elderly patient), severe abdominal pain, distension,
and partial ileus is present in approximately one-third of patients.
- Fulminant disease is the most severe form of CDI and develops in 1% to 3% of cases.
Defined as severe disease complicated by hypotension or shock, toxic megacolon,
perforation, or severe colitis on CT scan, it is associated with high mortality (40). The
first warning sign of fulminant colitis may be diminishing diarrhea, due to decreased
colonic muscle tone. A study of 44 patients undergoing colectomy for fulminant
colitis reported that 5 (11%) presented with frank peritonitis, hypotension, or both
(40). Thirty-five percent of patients with fulminant colitis caused byC. difficilewere
diagnosed at autopsy (40), suggesting that a significant number of deaths due to
“sepsis” in critically ill patients may be related toC. difficile.
Characteristic laboratory findings include leukocytosis that may be severe and
hypoalbuminemia. WBC counts as high as 50,000 cells/mL can be seen and band forms are
frequently present. One prospective study of 400 inpatients found CDI in 11% of those with
WBC of 15 to 19,900 cells/mL, 15% of those with WBC 20 to 29,000 cells/mL, and 34% of those
with WBC30,000 cells/mL (41). Hypoalbuminemia is the result of large protein losses
attributable to leakage of albumin and may occur early in the course of the disease (25).
PMC is seen in moderate to severe cases of CDI. Evidence of colitis includes fever,
abdominal cramps, leukocytosis, and presence of leukocytes in the feces. Endoscopic
Table 2 Definition ofClostridium difficileinfection
- Presence of symptoms
3 unformed stools over 24 hours for at least 2 days in the absence of ileus
and
- Positive stool test for the presence of toxigenicClostridium difficileor its toxins
or - Colonoscopy revealing pseudomembranes
276 Hjalmarson and Gorbach