Page 978 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 76: Gastrointestinal Infections and Clostridium Difficile 709

similarly challenges our understanding of the pathophysiology of these
infections.
■ CLINICAL PRESENTATION

The clinical presentation of patients with C difficile can be quite diverse.
In addition to asymptomatic carriage, some patients may report only
a minimal increase in the frequency or liquidity of bowel movements.
Such individuals, while at low risk of complication from infection, if
not identified and appropriately isolated from other patients, represent
a potentially important reservoir for the spread of C difficile within
the ICU. At the other extreme, patients may experience severe clinical
deterioration as a result infection with C difficile. The bowel movements
of the patient with C difficile infection may be watery and voluminous,
such as is seen in noninflammatory diarrheas. Other patients with
C difficile infection experience a clinical syndrome more consistent
with that of the inflammatory gastroenteritis, occasionally even report-
ing gross blood in the stool. Fever is present in about half of patients.
Leukocytosis, sometimes profound, is often a reliable indicator of the
onset of C difficile colitis. Clinicians should consider testing for CDI in
the setting of unexplained leukocytosis. In rare cases, CDI can cause
pouchitis or ileitis in patients who have previously undergone a total
colectomy. Symptoms of CDI usually begin soon after colonization, with
a median time to onset of 2 to 3 days but it is important to understand
the risk of CDI can persist for many weeks after antibiotics are stopped. 28
In extreme cases, patients infected with C difficile present with the FIGURE 76-1. Pseudomembranous colitis on colonoscopy. Used with permission of
complication of toxic megacolon. Such patients may or may not experi- Dr David T. Rubin, The University of Chicago Medicine, Chicago, Illinois.
ence diarrhea. Abdominal radiography in these cases reveals grossly
dilated colonic loops without evidence of mechanical obstruction. The
patients frequently demonstrate end-organ dysfunction as is typical for or its toxin or colonoscopic or histopathological findings demonstrating
the sepsis syndrome. The diagnosis of toxic megacolon carries with it a pseudomembranous colitis (see Fig. 76-1). In the rare cases in which
high degree of mortality. Colonic perforation can result if the infection patients will present with colonic distension and ileus but no diarrhea,
is not treated promptly. the diagnosis is especially difficult. Current SHEA/IDSA guide-
■ MICROBIOLOGY lines recommend testing for C difficile or its toxins only on diarrhea
28
C difficile is an obligate anaerobic gram-positive bacillus whose viru- (unformed stools), unless ileus is suspected. Testing in asymptomatic
individuals is not useful, including testing for cure. Repeat testing dur-
lence is attributed to the production of extracellular toxins. C difficile ing the same diarrheal episode is also not clinically useful. 32
can be identified as part of the normal flora in patients without overt The optimal diagnostic strategy for CDI that is timely, cost-effective,
diarrheal disease. In these individuals, toxin-negative strains of C dif- and accurate still remains somewhat controversial. Previously, the gold
ficile are likely no more than harmless commensal organisms. In fact, standard for diagnosis was the cytotoxic assay. With this study, diluted
there are data suggesting that progression to diarrhea occurs early after stool is added to monolayers of cultured cells. Observation of a cytopathic
acquisition of C difficile or not at all. To produce diarrhea and other effect that is neutralized by antibody against the toxins is more than 95%
35
manifestations of clinical disease, infecting strains of C difficile must sensitive and specific for the identification of toxigenic C difficile.
40
produce extracellular toxins. Together, toxin A (enterotoxin) and toxin However, this method is time consuming and beyond the technical
B (cytotoxin) cause epithelial cell necrosis through the disruption of the capacity of many labs, rendering it impractical for general use. Similarly,
actin cytoskeleton. More recently, strains of toxin A–negative, toxin detection of C difficile in stool culture followed by the identification of
37
B–positive C difficile have been described in association with outbreaks a toxigenic isolate (cytotoxic culture) or by cell cytotoxicity assay is also
of hospital-acquired disease. 38 not useful clinically because of the slow turnaround time of both tests.
■ DIAGNOSIS Testing by enzyme immunoassay (EIA) was developed to detect toxin
A or toxins A and B. This test has been adopted by many hospitals in
The spectrum of clinical disease associated with C difficile infection the United States because results are rapidly available and it has lower
makes diagnosis solely on the basis of clinical observations impractical. cost than many other modalities. However, a major drawback of this
That said, experienced clinicians often point to what they consider to be testing method is the diminished sensitivity (63%-94%) and specificity
a typical picture of C difficile diarrhea, including foul-smelling stool that (75%-100%) of this approach. A different strategy using a two-step
is greasy and green in color. Unfortunately, such observations are actu- method is becoming more frequency used. Stool samples are first
ally of limited value. On the other hand, readily available historical data, screened using EIA to detect glutamate dehydrogenase (GDH). If posi-
when accurately obtained, can be far more informative in leading the tive, the samples are then sent for a confirmatory test using either cell
clinician to an accurate diagnosis. The onset of diarrhea due to C difficile cytotoxic assay or toxigenic culture. Although this approach has a high
infection most commonly occurs in close relation to antibiotic adminis- negative predicative value and is an improvement from EIA testing for
tration. Twenty-five percent of cases present while dosing is ongoing. toxin, some studies have questioned the test’s sensitivity, which can vary
39
However, both the published literature and clinical experience reveal based on which commercial kit is used. 28,41,42 A final method with prom-
episodes of C difficile colitis that occur within 48 hours of the initiation ise is real-time polymerase chain reaction (RT-PCR), which is highly
of antibiotic therapy, and others that develop months after exposure. sensitive and specific. This approach uses nucleic acid amplification
The diagnosis of CDI is based on clinical and laboratory findings, techniques to detect the presence of toxin genes from stool. Although
which include the following: (1) the presence of diarrhea, defined as the test is highly sensitive, specific, and rapid, cost may limit its use. But
passage of three or more unformed stools in 24 or fewer consecutive when widely available, PCR may prove to be the most reasonable modal-
hours, (2) a positive stool test result for the presence of toxigenic C difficile ity to help diagnose CDI.

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