Infectious Diseases in Critical Care Medicine

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  1. Polymerase chain reaction (PCR)is very sensitive but requires significant technical
    expertise. However, a rapid detection method developed in Spain using nested PCR
    of the toxin B genes has been found to be 96% sensitive and 100% specific, and can be
    performed in several hours (3). PCR assays are not yet widely available for routine
    use, but three companies are preparing to release PCR test kits by 2009.


Two-Step Protocol
To improve the laboratory diagnosis of CDI, the Infectious Diseases Society of America (IDSA)
and the Society for Hospital Epidemiology of America (SHEA) are recommending a two-step
test (45).
The first step uses a test with high sensitivity, such as the common-antigen assay (GDH)
or stool culture, as a screening test to excludeC. difficilein the 75% to 90% of stool specimens
that do not containC. difficile. In the second step, positive specimens are analyzed for the
presence of toxins A and B with either tissue culture cytotoxin assay or EIA as a confirmatory
test. A study by Ticehurst (46) indicate that this two-step method has good sensitivity,
specificity, and cost although there is a 24-to 48-hour delay in reporting results.
The diagnosis of CDI should be based on determination of the presence of toxin A and/
or B in stool samples in concert with clinical suspicion for presence of the disease. Stool tests
forC. difficiletoxins should be avoided in cases without clinically compatible picture since
toxin positivity without clinical symptoms usually represents mere colonization with a
toxigenic strain ofC. difficile, which does not warrant treatment.Once a stool sample has been
demonstrated to contain toxin, repeat testing (e.g., performing a “test of cure” at the end of
therapy) is unnecessary because the EIA can remain positive for weeks to months in clinically
cured patients (45).


TREATMENT
General Treatment Guidelines
The most important step in the treatment for CDI is the withdrawal of the offending antibiotic
as soon as possible. If continued antibiotics are necessary, it is recommended to choose agents
with low probability of causing CDI, such as tetracycline, narrow-spectrum b-lactams,
piperacillin-tazobactam, macrolides, sulfonamides, aminoglycosides, vancomycin, metronida-
zole, and trimethoprim-sulfamethoxazole whenever possible. Supportive measures such as
intravenous fluid and electrolyte replenishment should be instituted if necessary. Use of
antiperistaltic agents, such as narcotics and loperamide, should be avoided as they may
promote the development of toxic megacolon (6).


Antibiotic Treatment—History
In the 1950s, when AAD became a well-known complication to antibiotic use,S. aureuswas the
presumed pathogen and oral vancomycin became the standard treatment.C. difficilewas
discovered as the organism causing CDI in 1978 and shortly thereafter oral vancomycin was
approved by the U.S. Food and Drug administration (FDA) for treatment of CDI. Vancomycin
remains the only drug that has been FDA approved for treatment of CDI. In the 1980s, studies
suggested that metronidazole was equally effective compared with vancomycin in the treatment
of CDI (47). In addition, metronidazole was less expensive and perhaps less likely to lead to the
development of vancomycin-resistant enterococci (VRE). The 1995 guidelines from the Centers
for Disease Control and Prevention (CDC), IDSA, and SHEA recommend the use of
metronidazole as first-line treatment of CDI. Since then, two prospective randomized trials
(48,49) have shown that oral vancomycin is superior to metronidazole in severe CDI while there
was a trend of vancomycin being more efficacious in mild and moderate disease. In the 2003
outbreak of the epidemic strain B1/NAP1 in Quebec, initial treatment with oral vancomycin
was associated with a 79% lower risk of complicated CDI compared with metronidazole.


Vancomycin and Metronidazole-Pharmacology
CDI, a toxin-mediated disease, is caused whenC. difficilespores in the colon transform to the
vegetative form and produce toxin A and B. To effectively treat the disease the antibiotic needs
to reach the colonic lumen.


280 Hjalmarson and Gorbach

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