Legionnaires Disease Workup

While pneumonias caused by numerous pathogens share similar laboratory findings, hyponatremia (sodium < 130 mEq/L) secondary to the syndrome of inappropriate antidiuretic hormone (SIADH) is more common in Legionnaires disease (LD) than in pneumonias secondary to other pathogens; however, this is not specific for LD.

Other nonspecific laboratory findings in LD include the following:

• Early/mildly elevated liver enzymes

• Highly elevated erythrocyte sedimentation rate (ESR) (>90 mm/h)

• Highly elevated ferritin levels (>2 times normal)

• Increased C-reactive protein (CRP) levels (>30 mg/L)

• Hypophosphatemia (specific to LD excluding other causes of hypophosphatemia) ^[13]

• Microscopic hematuria

Severe disease is defined by respiratory failure, bilateral pneumonia, rapidly worsening pulmonary infiltrates, or the presence of at least 2 of the following 3 characteristics:

• Blood urea nitrogen (BUN) greater than or equal to 30 mg/dL

• Diastolic blood pressure lower than 60 mm Hg

• Respiratory rate greater than 30/min

Typically, legionellae histopathologic lesions are found in interstitial lining and alveoli with polymorphonuclear cells and macrophages.

General tests in LD can include the following:

• Complete blood count (CBC): Look for leukocytosis, left shift

• Look for elevated ESR

• Electrolytes: Look for hypophosphatemia and hyponatremia

• BUN and creatinine: Look for renal failure and dehydration

• Liver function tests (LFTs): Look for nonspecific LFT abnormalities, which are very common in LD and may help to distinguish it from other atypical pneumonias

• Look for highly elevated serum ferritin

• Creatine phosphokinase: Look for elevation indicating rhabdomyolysis, which occasionally is seen in LD; the rhabdomyolysis may be so severe as to cause renal failure

• Arterial blood gas (ABG): Look for hypoxemia

• Gram stain: Typically, many leukocytes and a paucity of organisms are observed; if visible, the organisms are small, faintly staining, gram-negative bacilli

• Sputum Gram stain: Look for increased polymorphonuclear leukocytes and monocytes without bacteria

• Urinalysis: Look for proteinuria, hematuria, and renal failure

Culture of respiratory secretions

The definitive method for diagnosing Legionella is isolation of the organism in the respiratory secretions (ie, sputum, lung fluid, pleural fluid). However, Legionella species do not grow on standard microbiologic media but instead require buffered charcoal yeast extract (CYE) agar and cysteine for growth. Optimal growth occurs at 35-37°C.

Legionella is a slow-growing organism and can take 3-5 days to produce visible colonies. The organisms typically have a ground-glass appearance.

Routine sputum cultures have a sensitivity and specificity of 80% and 100%, respectively. Transtracheal aspiration of secretions or bronchoscopy specimen increases the sensitivity. Bronchoalveolar lavage (BAL) fluid provides a higher yield than bronchial wash specimens.

Blood cultures

Legionella can be isolated from blood, but it shows a much lower sensitivity.

Amplification with PCR assay

Polymerase chain reaction (PCR) assay of urine, serum, and bronchiolar lavage fluid is very specific for the detection of legionellae, but the sensitivity is not greater than that of culture. The primary benefit of this procedure, like IFA titers, is that it can be used to detect infections caused by legionellae other than L pneumophila serogroup 1.

Direct fluorescent antibody staining of sputum

Direct fluorescent antibody staining (DFA) is a rapid test that yields results in 2-4 hours, but it has a lower sensitivity and has fallen out of favor. The specificity of DFA is 96-99% using monoclonal antibody instead of polyclonal antibody.

A positive result depends on finding large numbers of organisms in the specimen; therefore, the sensitivity is increased when samples from the lower respiratory tract are used. DFA results rapidly become negative (in 4-6 d).

Serology

The most widely used tests include the immunofluorescent antibody (IFA) and enzyme-linked immunosorbent assay (ELISA) tests. A single increased antibody titer confirms LD if the IFA titer is greater than or equal to 1:256.

While LD serologic tests are the most readily available, they require a 4-fold increase in antibody titer (to 1:128 or greater), which takes 4-8 weeks. Paired measurements from both the acute and convalescent periods should be obtained, since an antibody response may not be apparent for up to 3 months. Of note, antibody levels do not increase in approximately one third of patients with LD.

Urinary antigen testing

The Legionella lipopolysaccharide antigen is detected with ELISA, radioimmunoassay (RIA), and the latex agglutination test. The Legionella lipopolysaccharide antigen becomes detectable in 80% of patients on days 1-3 of clinical illness. The urinary antigen assay can be used to detect only L pneumophila (serogroup 1). ^[14]

The advantages of urinary antigen testing include rapidity and simplicity. In addition, the relative ease of obtaining a urine sample compared with obtaining sputum specimens and the persistence of antigen secretion in patients who are on antibiotic therapy increase the usefulness of the urine antigen detection method. ^[14]

The urinary antigen test may initially be negative, but when positive it can remain positive for months after the acute episode has resolved. ^[14]

Radiography

Legionella infection almost always produces an abnormal chest radiographic finding, with the abnormalities typically being unilateral and occurring in the lower lobes. However, the abnormalities are variable and may be focal or diffuse; no typical radiographic presentation exists for LD. ^[15]

Rapidly progressive, asymmetrical infiltrates are nonetheless characteristic of the disease. Chest radiography often shows patchy alveolar infiltrates with consolidation in the lower lobe (although all lobes may be affected). Progression of the infiltrates may be seen despite antibiotic therapy. Up to 50% of patients have a pleural effusion. Cavity and abscess formation are rare in LD but can occur in immunocompromised hosts.

Improvement revealed on chest radiography can lag behind clinical improvement by 5-7 days; the radiographic abnormalities can take up to 3-4 months to resolve completely.

Noncontrast head CT scanning

Noncontrast head computed tomography (CT) scanning is indicated for patients with altered mental status. Findings should be normal in LD.

Bronchoscopy

Bronchoscopy with or without BAL may be helpful in establishing or excluding the diagnosis if respiratory culture specimens are difficult to obtain. BAL fluid gives a higher yield than bronchial wash specimens.

Lumbar puncture

This procedure is indicated for patients with altered mental status. In uncomplicated LD, the cerebrospinal fluid (CSF) findings are generally normal.

Thoracentesis

If a pleural effusion is present, fluid can be evaluated using DFA or LD culture.