Legionnaires Disease Workup
- Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD more...
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) 
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.
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.
Legionella can be isolated from blood, but it shows a much lower sensitivity.
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).
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).
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.
The urinary antigen test may initially be negative, but when positive it can remain positive for months after the acute episode has resolved.
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.
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.
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 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.
This procedure is indicated for patients with altered mental status. In uncomplicated LD, the cerebrospinal fluid (CSF) findings are generally normal.
If a pleural effusion is present, fluid can be evaluated using DFA or LD culture.
Kozak-Muiznieks NA, Lucas CE, Brown E, Pondo T, Taylor TH Jr, Frace M, et al. Prevalence of sequence types among clinical and environmental isolates of Legionella pneumophila serogroup 1 in the United States from 1982 to 2012. J Clin Microbiol. 2014 Jan. 52(1):201-11. [Medline]. [Full Text].
Nguyen TM, Ilef D, Jarraud S, Rouil L, Campese C, Che D. A community-wide outbreak of legionnaires disease linked to industrial cooling towers--how far can contaminated aerosols spread?. J Infect Dis. 2006 Jan 1. 193(1):102-11. [Medline].
Woo AH, Goetz A, Yu VL. Transmission of Legionella by respiratory equipment and aerosol generating devices. Chest. 1992 Nov. 102(5):1586-90. [Medline].
Brandsema PS, Euser SM, Karagiannis I, DEN Boer JW, VAN DER Hoek W. Summer increase of Legionnaires' disease 2010 in The Netherlands associated with weather conditions and implications for source finding. Epidemiol Infect. 2014 Jan 24. 1-12. [Medline].
Halsby KD, Joseph CA, Lee JV, Wilkinson P. The relationship between meteorological variables and sporadic cases of Legionnaires' disease in residents of England and Wales. Epidemiol Infect. 2014 Jan 9. 1-8. [Medline].
Cristino S, Legnani PP, Leoni E. Plan for the control of Legionella infections in long-term care facilities: Role of environmental monitoring. Int J Hyg Environ Health. 2011 Sep 16. [Medline].
Lin YE, Stout JE, Yu VL. Controlling Legionella in hospital drinking water: an evidence-based review of disinfection methods. Infect Control Hosp Epidemiol. 2011 Feb. 32(2):166-73. [Medline].
van Loenhout JA, van Tiel HH, van den Heuvel J, Vercoulen JH, Bor H, van der Velden K, et al. Serious long-term health consequences of Q-fever and Legionnaires' disease. J Infect. 2014 Jan 25. [Medline].
Cunha BA. Hypophosphatemia: diagnostic significance in Legionnaires' disease. Am J Med. 2006 Jul. 119(7):e5-6. [Medline].
Kashuba AD, Ballow CH. Legionella urinary antigen testing: potential impact on diagnosis and antibiotic therapy. Diagn Microbiol Infect Dis. 1996 Mar. 24(3):129-39. [Medline].
Tan MJ, Tan JS, Hamor RH, File TM Jr, Breiman RF. The radiologic manifestations of Legionnaire's disease. The Ohio Community-Based Pneumonia Incidence Study Group. Chest. 2000 Feb. 117(2):398-403. [Medline].
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1. 44 Suppl 2:S27-72. [Medline].
Cunha BA. Legionnaires' disease: clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am. 2010 Mar. 24 (1):73-105. [Medline].
Cunha BA, Strollo S, Schoch P. Extremely elevated erythrocyte sedimentation rates (ESRs) in Legionnaires' disease. Eur J Clin Microbiol Infect Dis. 2010 Dec. 29 (12):1567-9. [Medline].
Cunha BA. Highly elevated serum ferritin levels as a diagnostic marker for Legionella pneumonia. Clin Infect Dis. 2008 Jun 1. 46 (11):1789-91. [Medline].
|Diagnostic Predictors||Diagnostic Eliminators|
|Laboratory Predictors b
|Legionnaire disease very likely if >3 predictors present||Legionnaires disease very unlikely if <3 predictors or >3 diagnostic eliminators present|
|Abbreviations: CPK = creatinine phosphokinase test; CRP = C-reactive protein; ESR = erythrosedimentation rate.
a Pulmonary symptoms: shortness of breath, cough, and so forth with fever and a new focal/segmental infiltrate on chest radiograph.
b Otherwise unexplained. If finding is due to an existing disorder, it should not be used as a clinical predictor.