Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (465 page)

Serology
: Serologic testing is not helpful for the diagnosis of acute genital infection caused by
C. trachomatis
. Serology may be useful to document diagnosis of psittacosis, LGV, and respiratory tract infections.

   
Complement fixation
(
CF
)
assays
target response to LPS common to all members of the Chlamydiaceae, so positive results must be interpreted in the context of disease. CF testing is most useful for LGV, where titers ≥256 are considered diagnostic.

   
Microimmunofluorescence
(
MIF
)
assays
are useful for the diagnosis of neonatal pulmonary infection because they allow specific detection of IgM and IgG. An IgM titer of ≥32 supports the diagnosis. In LGV, an IgG titer of ≥128 provides strong support for diagnosis.
Chlamydophila pneumoniae
infection may be documented by a fourfold increase in titer between acute and convalescent specimens, an IgM titer ≥16 or an IgG titer ≥512.

   
EIA assays
, based on synthetic peptides, have been developed to simplify the technically demanding MIF procedure. In general, results have compared favorably to results of MIF testing.

CLOSTRIDIAL INFECTIONS: GENERAL

Clostridium
species are anaerobic, spore-forming gram-positive bacilli. The formation of spores results in efficient survival of clostridia in the environment; the spores serve as the source of infections of exogenous origin (e.g.,
Clostridium difficile
colitis,
Clostridium perfringens
food poisoning). Clostridia may also cause infections of endogenous origin (e.g., myonecrosis).
Clostridium
species produce some of the most potent toxins, which are responsible for some clostridial diseases (e.g., tetanus). Botulinum toxin is considered to have significant potential for use as a bioterror agent.

Clostridia grow well and rapidly on media for anaerobic culture, but selective media may be needed for contaminated specimens. The interpretation of cultures positive for
Clostridium
species is usually straightforward, but because of the ubiquitous distribution of clostridia in the environment, positive cultures must be interpreted in the context of the clinical presentation. Standardized susceptibility testing is available using specialized techniques, but many laboratories do not offer the testing in-house.

CLOSTRIDIAL GAS GANGRENE, CELLULITIS, AND PUERPERAL SEPSIS

   Definition

These syndromes may be caused by a number of clostridial species of endogenous or exogenous origin. Most cases of clostridial gangrene are caused by
C. perfringens
,
Clostridium novyi,
and
Clostridium septicum
.

   Who Should Be Suspected?

Patients present with rapidly progressive tissue necrosis, tissue liquefaction, and gas formation. Gas formation in tissue is not specific for clostridial infections and may be formed by other bacterial pathogens. Clostridial myonecrosis should be considered a medical emergency, and rapid and effective communication with clinical personnel, especially surgeons, is critical.

   Laboratory Findings

Direct detection
: Gram stain typically shows massive tissue necrosis, a lack of PMNs, and the presence of typical organisms (usually large “box-car” GPBs; the absence of spores on Gram stain is common and does not rule out clostridial infection; other bacterial morphotypes may be seen in mixed infections).

Culture
: Blood cultures may be positive.

Core laboratory
: WBC count is increased (15,000–40,000/μL). Platelets are decreased in 50% of patients. Protein and casts are often present in urine. Renal insufficiency may progress to uremia. Laboratory findings typical for underlying diseases (e.g., DM) or complications of clostridial infection are seen. In postabortion sepsis, sudden severe hemolytic anemia is common with conditions such as hypoglobulinemia, hemoglobinuria, increased serum bilirubin, spherocytosis, and increased osmotic and mechanical fragility.

CLOSTRIDIUM DIFFICILE
INFECTION (CDI) AND ASSOCIATED (PSEUDOMEMBRANOUS) COLITIS

   Definition

Clostridium difficile
is a major cause of antibiotic-associated diarrhea and colitis. It is the most important cause of pseudomembranous colitis. CDI is usually acquired nosocomially.

   Who Should Be Suspected?

Several factors are associated with increased risk for
C. difficile
disease, including recent or current antimicrobial (or antineoplastic) therapy, age (>65 years), suppression of gastric acid production, and debilitating underlying medical conditions.

   Laboratory Findings

Culture
: Specific laboratory diagnosis is based on the growth of
C. difficile
from stool culture or by detection of
C. difficile
–specific antigen, toxins, or DNA. Testing should be performed only on liquid stool specimens; asymptomatic carriage may be seen. Formed stool should be rejected if submitted for testing. Isolation of toxigenic
C. difficile
, using selective anaerobic culture, is considered the “gold standard” for diagnosis. Toxin production by isolates must be documented and may be confirmed by PCR, antigen, or cytotoxicity assays. The complexity and turnaround time required for toxigenic culture assays have limited their use for routine testing.