Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (579 page)

The pulmonary signs and symptoms of
Legionella
pneumonia are fairly nonspecific and are characterized by progressive respiratory distress (dyspnea, cough, and minimal sputum production). Symptoms outside the respiratory tract may increase the likelihood of legionellosis. GI symptoms, including diarrhea, nausea and vomiting, hepatic dysfunction, and abdominal pain, occur frequently and may be prominent. Patients often develop confusion or other neurologic findings. Hyponatremia occurs more frequently in legionellosis and in other types of pneumonia.

   Laboratory Findings

Specific diagnosis is most reliably based on culture isolation and antigen detection.

Culture
: Isolation requires the use of special media, usually a combination of selective and nonselective buffered charcoal yeast extract (BCYE) agars. Using pleural fluid, lung biopsy, or transtracheal or bronchial aspirate, organisms may require 3–7 days’ incubation for isolation.

Direct antigen detection and serology
: Urine antigen testing is an important method for diagnosis of Legionnaires diseases caused by
L. pneumophila
serogroup 1 (approximately 90% of community-acquired and approximately 60% of nosocomial respiratory
Legionella
respiratory infections). The specificity of the urine antigen test is approximately 99%. Antigen may be detected in urine for several days after the initiation of antimicrobial therapy. The sensitivity of urine antigen testing depends on the probability of infection with
L. pneumophila
serogroup 1 and the severity of infection. About 90% of patients with severe legionellosis that requires hospitalization should show a positive urine antigen test, whereas only about 50% of outpatients with milder legionellosis will yield a positive urine antigen test. The specificity of the urine antigen test is approximately 99%.

Serologic testing may be a useful adjunct to diagnostic testing, but serologic testing plays a limited role in acute patient management because of the time required to provide definitive results. Serum IFA testing is recommended and allows detection of immunoglobulin subclasses. Testing for total antibody as well as specific IgM and IgG is recommended. Seroresponse may not be detectable for weeks to months after acute infection. Only half of infected patients will seroconvert at 2 weeks. Therefore, testing paired acute and multiple convalescent (2, 4, 6, 8, and 12 weeks) serum samples is recommended. A diagnosis is supported by detection of specific IgM or by a fourfold or greater change in titer between acute and convalescent specimens. Specificity depends on the antigen preparation used in the assay. Tests that use
L. pneumophila
serogroup 1 demonstrate the best specificity (approximately 99%), while assays that use polyvalent antigen preparations demonstrate somewhat lower (90–95%) specificity.

Direct detection
: Gram stain of sputum is of little use for detection because the faintly staining organisms are frequently masked by the proteinaceous background. Patient specimens show few to moderate number of PMNs. Stains with enhanced staining of
Legionella
, like silver or Gimenez staining, also show poor overall sensitivity for detection of legionellosis. DFA staining is very specific but shows variable sensitivity (25–75%). Therefore, a negative DFA test result cannot rule out legionellosis and does not substitute for culture.

Molecular testing
: PCR-based assays have been described, but FDA-approved tests are not available. Molecular assays have not been shown to be superior to culture for the diagnosis of
Legionella
infection.

Published assays show moderate to high sensitivity, depending on the type of specimen tested, and high specificity. An advantage of most molecular diagnostic tests, compared to the urine antigen assay, is their ability to detect all
Legionella
species, rather than being limited to
L. pneumophila
serogroup 1.

Core laboratory findings
: WBC count is increased (10,000–20,000/μL) in 75% of cases (leukopenia is a bad prognostic sign); thrombocytopenia is common. Hypophosphatemia; hyponatremia; hypoalbuminemia (<2.5 g/dL); proteinuria (approximately 50% of patients); microscopic hematuria; and abnormal LFTs (mild to moderate increase of serum AST, ALP, LD, or bilirubin is found in approximately 50% of patients).

Suggested Readings

Fields BS, Benson RF, Besser RE. Legionella and Legionnaires’ disease: 25 years of investigation.
Clin Microbiol Rev.
2002;15:506–526.

Newton HJ, Ang DKY, van Driel IR, et al. Molecular pathogenesis of infections caused by
Legionella pneumophila
.
Clin Microbiol Rev.
2010;23:274–298.

BACTERIAL PNEUMONIA

   Definition

Pneumonia describes infection of the pulmonary parenchyma. Bacteria most commonly gain access to lower respiratory tract directly, by inhalation or aspiration, or by hematogenous seeding from a distal site of infection.
Streptococcus pneumoniae
is the most common cause of serious community-acquired bacterial pneumonia. Viruses are implicated in about 30% of cases of communityacquired pneumonia. Other pathogens, like
H. influenzae, Moraxella catarrhalis, M. pneumoniae, Legionella,
and
C. pneumoniae
, are also significant pathogens.
Staphylococcus aureus
and gram-negative bacilli are often implicated in nosocomial pneumonias.

   Who Should Be Suspected?

   A broad range of conditions predispose to bacterial pneumonia, including underlying medical conditions (e.g., alcoholism, decreased level of consciousness, malnutrition, immune compromise, uremia), toxic exposure (e.g., inhalants, tobacco smoke, environmental pollutants), structural or functional defects of normal pulmonary defense mechanisms (e.g., COPD, cystic fibrosis, bronchiectasis, ciliary dysfunction), and age >65 years.

   Common symptoms include dyspnea, shortness of breath, pleuritic chest pain, cough, and sputum production, typically purulent. Systemic signs include fever and malaise; a significant minority of patients report rigors.

   Physical examination may demonstrate diffuse or localized abnormalities, including rales, ronchi, and diminished breath sounds.

   Diagnostic and Laboratory Findings

   Pneumonia is generally diagnosed on the basis of clinical signs and symptoms and CXR.