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CHAPTER 104: Jaundice, Diarrhea, Obstruction, and Pseudoobstruction 1003

beneficial effects in the host. Prebiotics are nondigestible food ingredi- reduced time from the development of symptoms to severe disease and
ents that beneficially affect the host by selectively stimulating the growth thus require more aggressive therapy and monitoring. 70,71
or activity of one or a limited number of bacteria in the colon, and thus Identified risk factors for the development of CDI include age ≥65 years,
improve the health of the host. Synbiotics are a combination of prebiotics increased duration of hospitalization, exposure to antimicrobial agents
and probiotics able to modulate gut immunity and facilitate nutrient/ (with longer exposure and exposure to multiple antimicrobials increas-
factor interaction necessary for gut recovery. A review of the literature ing this risk), cancer chemotherapy, gastrointestinal surgery, and gastric
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by Isakow in 2007 found no evidence for the use of probiotics in acid suppression. 43,68 Prognostic factors for poor outcome following CDI
critically ill patients. The SCCM/ASPEN Clinical Practice Guidelines include advanced age, comorbidities, decreased antibody response to the
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published in 2009 state there exist insufficient data to make recommen- infection, gastric acid suppressants, the need to prolong inciting antibi-
dations for general usage in the ICU population. There are currently otic therapy, immunodeficiency, and ICU admission. 62,71
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a number of active trials investigating their use in the ICU population. Clinical Presentation of Clostridium Difficile: CDI symptoms present at
Finally, the method of delivering enteral feeds can also cause diarrhea a median of 2 to 3 days after colonization. Typical clinical features
with continuous feeding potentially having a lower incidence compared consist of watery, grossly nonbloody diarrhea and abdominal pain.
with intermittent feeding. 57,58 Bacterial contamination of enteral feeds Systemic features can include fever, anorexia, nausea, malaise, and
has also been postulated as a cause of diarrhea although data for this a leukocytosis. Severe disease can develop a colonic ileus and toxic
are lacking. 34 dilation with minimal or no diarrhea. Complications of CDI include
■ CLOSTRIDIUM DIFFICILE dehydration, electrolyte imbalances, hypoalbuminemia, renal failure,
toxic megacolon, colonic perforation, SIRS, sepsis, shock, and death.
The Clostridium difficile bacillus was first described in 1935, although Fulminant colitis occurs in 1% to 3% of patients and the hospital
its association with disease was not identified until 1978. Clostridium mortality associated with toxic megacolon is reported as 24% to 38%. 64,72
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difficile infection (CDI) has become an increasingly common cause of Diagnosis of Clostridium Difficile: Diagnosis is made based on a com-
health care–associated diarrhea and an increasingly common reason for bination of clinical and laboratory information. Recently published
admission to the intensive care unit (ICU). 60-63 US and European guidelines have better defined this disease and its
The prevalence of asymptomatic colonization with C difficile is 7% to treatment. 43,71,73 CDI is defined by the presence of symptoms (usually
26% among adult inpatients in acute care facilities. The primary reser- diarrhea) and either a stool test positive for C difficile toxins or toxigenic
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voirs of C difficile are colonized or infected patients and contaminated C difficile, or colonoscopic or histopathologic findings revealing pseu-
environments and surfaces within hospitals. Recently, there have been domembranous colitis. Laboratory testing should only be performed on
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major outbreaks of CDI in North America, England, Europe, and Asia, diarrheal stool unless ileus due to CDI is suspected, and it is not recom-
and the emergence of more virulent strains is leading to greater numbers mended to test asymptomatic patients or use as a test of cure. Although
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of infected patients with greater disease severity and mortality. 63,65-67 stool culture is the most sensitive test, it requires 2 to 3 days for results.
Enzyme immunoassays (EIA) for toxin are rapid but have historically
Pathogenesis of Clostridium Difficile: C difficile is an anaerobic gram- had poor sensitivity. However, newer EIA and polymerase chain reac-
positive spore-forming bacillus that most commonly exists in a veg- tion tests for toxin have high sensitivity and specificity rates. Since no
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etative form that is readily killed by even brief exposures to oxygen. testing strategy is 100% sensitive and specific, clinical suspicion and
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When in its spore form, it is heat stable and resistant to gastric acid consideration of patient risk factors remain important in making clinical
and many ethanol-based disinfectants. It is transmitted via the fecal- decisions about treatment. 43,71 This is particularly important for the up
oral route, from person to person and fomite to person. to 37% of fulminant CDI that present with ileus rather than diarrhea.
In healthy adults, the colon contains more than 500 species of bacteria, In CDI patients with ileus, and some with diarrhea, the diagnosis can
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some of which antagonize the adherence and proliferation of C difficile sometimes be made endoscopically. Pseudomembranes are islands of
in the colonic crypts. Creation of a suitable local environment allows neutrophils, fibrin, mucin, and cellular debris that can be appreciated
C difficile reproduction and the generation of toxins, thereby establish- histologically or on direct visualization via endoscopy. Of the patients
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ing CDI. The pathogenesis of CDI is dependent on the three events: who are diagnosed with combined laboratory and clinical criteria,
alteration of normal fecal flora, colonic colonization with toxigenic approximately 50% of these cases will have pseudomembranes on direct
C difficile, and growth of the organism and elaboration of its toxins. 64 visualization or on histopathologic examination, but the percentage
C difficile toxin A (enterotoxin) and B (cytotoxin) are both exotoxins. with pseudomembranes in severe disease can be as high as 85%. Thus,
Toxin B is more potent (up to 10×) than toxin A and demonstrates although endoscopy is not a sensitive test, the visualization of pseudo-
cytotoxic effects, but both cause increased vascular permeability by membranes is sufficiently specific to confirm the diagnosis of CDI.
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opening tight junctions between cells. They both induce the produc- Radiographic imaging may also provide information suggestive of
tion of TNF-α and proinflammatory cytokines which contribute to the CDI. Abdominal x-ray may show “thumbprinting” which is representa-
associated inflammatory response and formation of colonic pseudo- tive of colonic haustral thickening that can be seen in any form of colitis.
membranes. The majority of toxigenic C difficile strains produce both Abdominal computed tomography (CT) is a more sensitive test to assess
toxins, but approximately 1% to 2% of strains in the USA are negative for radiographic features of colitis (see Fig. 104-5). In the authors’
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for toxin A. 43 experience, an advantage of CT lies in its ability to help identify the
In 2002, hospitals in Quebec, Canada, began experiencing an epi- etiology of undifferentiated severe abdominal sepsis while confirmatory
demic of CDI with over 14,000 nosocomial cases reported between laboratory testing is pending. A patient hospitalized with new onset
2003 and 2004 with a mortality rate of almost 14% (historic controls abdominal sepsis, diarrhea, and pancolitis on CT scan has CDI until
had 2% mortality). 43,66 Similar outbreaks were also reported in a hand- proven otherwise and requires immediate empiric therapy.
ful of US states. In 2005, the NAP1/B1/027 epidemic strain of C difficile
was reported as the causative strain in these outbreaks with its increased Treatment of Clostridium Difficile
virulence traced to its ability to produce 16 × more toxin A and 23 × Medical Medical therapy for CDI largely revolves around antibiotic ther-
more toxin B than control strains, as well as uniformly carrying the gene apy and supportive care. The various society guidelines vary depending
for binary toxin. Further studies demonstrated this strain to have resis- on the severity of disease, with most recommending for severe cases
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tance to fluoroquinolone antibiotics that was new when compared to the use of oral vancomycin alone or in combination with intravenous
historic isolates. A recent assessment shows this strain has now spread metronidazole. There are also a number of other important aspects for
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to over 40 US states and 7 Canadian provinces, and caused outbreaks in CDI management. First, the inciting antibiotics should be discontinued
England, Europe, and Asia. 43,62,63 Infection with this strain may mean a if possible. In severe cases, empiric therapy should be initiated as soon as

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