Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (466 page)

Cytotoxicity assays
: These assays are based on detection of the cytotoxic effect of
C. difficile
toxin B on cultured eukaryotic cells. Testing may be performed on stool filtrate or
C. difficile
culture supernatant.

Toxin EIA
: A number of enzyme immunoassays are commercially available for rapid detection of
C. difficile
toxin B or both toxins A and B. Because of their simplicity and rapid turnaround time (<1 hour), EIA tests have been widely used for diagnosis of CDI. EIA assays have shown high specificity (>95%), but the sensitivity of different assays is variable, ranging from approximately 60 to 95%, which has limited their use in critically ill patients or infection control investigations.

Antigen detection
: Detection of
C. difficile
–specific glutamate dehydrogenase (GDH) antigen may be used to screen stools for
C. difficile
. The sensitivity of the GDH assay depends on the reference standard; sensitivities ranging from approximately 70 to >95% have been reported. Toxin must be documented in GDH antigen–positive specimens because nontoxigenic
C. difficile
strains are detected by this assay.

Molecular diagnostic testing
: PCR assays that target the toxin B gene have emerged as clinically important assays for the diagnosis of
C. difficile
GI infection. Several FDA-approved methods are commercially available. Reported performance of molecular diagnostic assays has shown S/S both in the range approximately 95–99%. The use of real-time PCR assays provides for results within 24 hours.

Combination tests
: Some laboratories have combined EIA, GDH antigen, and/ or PCR testing in simultaneous or sequential test algorithms to improve the S/S and cost-effectiveness of these test methods.

CLOSTRIDIUM TETANI
INFECTION

   Definition

Tetanus describes disease caused by a heat-labile toxin (tetanospasmin) elaborated by
Clostridium tetani
. Infection typically results from “dirty” traumatic injuries (e.g., deep puncture wounds, crush injuries) contaminated by spores of
C. tetani
. Toxin diffuses from the site of infection into the circulation, where it gains access to peripheral motor neurons. Toxin is transported through the neurons to the CNS, where it blocks inhibitory signals from the CNS to motor neurons. Tetanospasmin also binds to receptors at the myoneural junctions (different from the receptors for botulinum toxin), inhibiting the release of acetylcholine. Tetanus has been essentially eliminated in populations with an effective vaccination program, but sporadic cases occur in unvaccinated populations.

   Who Should Be Suspected?

Patients present with spasm of flexor and extensor muscles. Patients develop pathologic hyperresponsiveness to minor stimuli. Common features include “lock jaw,” risus sardonicus, and back spasms resulting in relentless arching.

   Laboratory Findings

Diagnosis is usually made on the basis of typical clinical findings. Culture from an infected site usually has poor sensitivity and is usually noncontributory. Core laboratory findings are usually normal.

DIPHTHERIA

See Chapter
13
, Respiratory, Metabolic, and Acid–Base Disorders.

ENTEROCOCCAL INFECTIONS

   Definition

Enterococcus
species are aerobic GPCs that form pairs and short chains.
Enterococcus
species are universal components of the endogenous lower GI tract flora in healthy humans; colonization of the urogenital mucosa is common. Enterococci are moderately virulent, but the mechanisms are not clearly understood.

Enterococci
may demonstrate intrinsic and acquired resistance to antibiotics, including vancomycin. This characteristic is at least partially responsible for the emergence of enterococci as significant nosocomial pathogens.
Enterococcus faecalis
and
E. faecium
are the species most commonly associated with human infection.

   Who Should Be Suspected?

Enterococci may cause infection in virtually any organ system; common infections include UTIs, bacteremia, endocarditis, intra-abdominal infections, and wound infections. Hospitalized patients who are rectal carriers of VRE may transmit these pathogens to other patients that may be at high risk for invasive VRE infection.

   Laboratory Findings

Culture
: Isolates grow in 24–48 hours on media for GPC isolation under standard incubation conditions. Susceptibility testing must be performed for significant clinical isolates.

ESCHERICHIA COLI
INFECTION

   Definition

Escherichia coli
is a nonfastidious, glucose-fermenting GNB.
E. coli
is the most common clinical isolate in most microbiology laboratories. It is a ubiquitous component of the GI bacterial flora and is the most common cause of community-acquired UTI in normal hosts.
Escherichia coli
is a major cause of nosocomial infections and infections in immunocompromised patients.
Escherichia coli
isolates may cause enteritis or gastroenteritis by a number of mechanisms, including toxin production and adherence to mucosal epithelial cells of the colon.

   Who Should Be Suspected?

Escherichia coli
should be considered in any patient with UTI.
Escherichia coli
may also be suspected in patients with “traveler’s diarrhea” (abrupt onset, with profuse, watery diarrhea after travel to an endemic area). Enterohemorrhagic
E. coli
infection may be suspected in patients with diarrhea, especially in patients who develop HUS after diarrheal illness. See the discussion of foodborne causes of diarrhea in Chapter
5
, Digestive Diseases.