examination reveals pseudomembranes in the colonic mucosa (see “Diagnosis”). PMC
primarily affects the large bowel, although the small intestine may rarely be involved.
The epidemic strain ofC. difficileB1/NAP1 has similar clinical features compared with
otherC. difficilestrains but causes more severe illness. Prominent complications include toxic
megacolon requiring colectomy, leukemoid reactions, septic shock, and death (10,11,37).
It is important to note that on rare occasion patients with severe CDI present without
diarrhea. This could imply paralytic ileus, which prevents the passage of stool. Symptoms such
as fever, leukocytosis, and abdominal pain in a patient with recent antibiotic exposure should
raise the suspicion of CDI even in the absence of diarrhea (25).
Extracolonic manifestations of CDI are very rare. The most commonly reported is
polyarthritis involving large joints occurring one to four weeks after infection (34). Case series
have described isolation ofC. difficile from pleural fluid, peritoneal fluid, blood, bone,
prosthetic joints, wounds (including necrotizing fasciitis), and splenic, vaginal, and perianal
abscesses. Generally, these infections are polymicrobial, making it difficult to ascertain the
pathogenic role ofC. difficile.
Relapsing CDI occurs in approximately 20% to 30% of appropriately treated infections.
The clinical presentation is usually very similar to the original presentation (42) and generally
occurs one to eight weeks, but usually within two weeks, after completion of anticlostridial
therapy.
DIFFERENTIAL DIAGNOSTIC CONSIDERATIONS
AAD is defined as otherwise unexplained diarrhea associated with antibiotic use. The majority
of the cases have no established microbial pathogen. A total of 15% to 25% of AAD result from
CDI and the likelihood for CDI increases with the severity of the illness. In 2% to 3% of AAD
cases pathogens such asC. perfringens, Klebsiella oxytoca, S. aureus, andCandida albicans(3,25).
have been isolated, but their significance remains questionable. In the remainder of the cases,
the etiology is unknown but may be due to osmotic diarrhea resulting from antibiotics
disturbing the normal bowel flora and cause failure to catabolize carbohydrates (25). The
breakdown of primary bile acids, which are potent colonic secretory agents, may also be
affected (26). In addition, certain antibiotics have direct effects on the gastrointestinal system.
For example, erythromycin increases the gastric emptying rate, clavulanate stimulates bowel
motility, and neomycin causes malabsorption (3).
The differential diagnosis for PMC includes intestinal obstruction, colon cancer,
leukemia, severe burns, shock, uremia, heavy metal poisoning, hemolytic-uremic syndrome,
Crohn’s disease, shigellosis, neonatal necrotizing enterocolitis, ischemic colitis, and Hirsch-
sprung’s disease. However, it is extremely uncommon to observe pseudomembranes in any of
the conditions listed above, with the exception of rare cases associated with heavy metal
poisoning and ischemic colitis. In the right clinical scenario, visualization of pseudomem-
branes during endoscopy is considered diagnostic of CDI (25).
Other possible alternative diagnoses to CDI are ulcerative colitis, typhlitis in neutropenic
patients, or diarrhea induced by medications such as laxatives, antacids, electrolyte
supplements (particularly magnesium), profilated nonsteroidal anti-inflammatroy drugs
(NSAIDS), contrast, products containing lactose or sorbitol, antiarrhythmic or cholinergic
medications.
DIAGNOSIS
Imaging Studies
Imaging studies have largely been replaced by laboratory testing as a tool for diagnosing CDI
(25). Radiologic studies are nonspecific but can support the diagnosis and are useful to monitor
for complications such as toxic megacolon and perforation.
Plain abdominal filmsmay reveal mucosal edema or paralytic ileus as well as detect free
intra-abdominal air and toxic megacolon. The presence of the “fingerprint sign” (showing a
patch of elevated and inflamed mucosa next to normal mucosa) is useful to diagnosis CDI.
Computed tomography (CT)can be valuable in the diagnosis of PMC or fulminant CDI.
Characteristic features include colonic wall thickening, pericolonic stranding, the accordion
sign, the double halo sign, and ascites (43). One study of 39 patients with CDI who underwent
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