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Legionnaires Disease Workup

  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Mar 30, 2016
 

Approach Considerations

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) [9]
  • 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
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Histologic Findings

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

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Laboratory Studies

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.

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).[10]

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.[10]

The urinary antigen test may initially be negative, but when positive it can remain positive for months after the acute episode has resolved.[10]

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.

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Imaging Studies

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.[11]

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.

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Procedures

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.

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Contributor Information and Disclosures
Author

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Frank C Smeeks, III, MD Specialty Medical Director of Emergency Medicine, Applied Medico Legal Solutions

Frank C Smeeks, III, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Association for Physician Leadership, American Medical Association, North Carolina Medical Society

Disclosure: Nothing to disclose.

Acknowledgements

Joseph F John Jr, MD, FACP, FIDSA, FSHEA Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Eric M Kardon, MD, FACEP Attending Emergency Physician, Georgia Emergency Medicine Specialists; Physician, Division of Emergency Medicine, Athens Regional Medical Center

Eric M Kardon, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Fred A Lopez, MD Associate Professor and Vice Chair, Department of Medicine, Assistant Dean for Student Affairs, Louisiana State University School of Medicine

Fred A Lopez, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, Infectious Diseases Society of America, and Louisiana State Medical Society

Disclosure: Nothing to disclose.

Scott Savage, DO Associate Clinical Faculty, Department of Emergency Medicine, Wright State University, Boonshoft School of Medicine

Disclosure: Nothing to disclose.

Lynn E Sullivan, MD Assistant Professor of Medicine, Yale University School of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jeter (Jay) Pritchard Taylor III, MD Compliance Officer, Attending Physician, Emergency Medicine Residency, Department of Emergency Medicine, Palmetto Health Richland, University of South Carolina School of Medicine; Medical Director, Department of Emergency Medicine, Palmetto Health Baptist

Jeter (Jay) Pritchard Taylor III, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

References
  1. 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].

  2. 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].

  3. Woo AH, Goetz A, Yu VL. Transmission of Legionella by respiratory equipment and aerosol generating devices. Chest. 1992 Nov. 102(5):1586-90. [Medline].

  4. 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].

  5. 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].

  6. 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].

  7. 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].

  8. 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].

  9. Cunha BA. Hypophosphatemia: diagnostic significance in Legionnaires' disease. Am J Med. 2006 Jul. 119(7):e5-6. [Medline].

  10. 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].

  11. 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].

  12. 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].

  13. Cunha BA. Legionnaires' disease: clinical differentiation from typical and other atypical pneumonias. Infect Dis Clin North Am. 2010 Mar. 24 (1):73-105. [Medline].

  14. 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].

  15. 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].

 
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This electron micrograph depicts an amoeba, Hartmannella vermiformis (orange), as it entraps a Legionella pneumophila bacterium (green) with an extended pseudopod. After it is ingested, the bacterium can survive as a symbiont within what then becomes its protozoan host. The amoeba then becomes a so-called "Trojan horse," since, by harboring the pathogenic bacterium, the amoeba can afford it protection. In fact, in times of adverse environmental conditions, the amoeba can metamorphose into a cystic stage, enabling it, and its symbiotic resident, to withstand the environmental stress. Image courtesy of the Centers for Disease Control and Prevention and Dr. Barry S Fields.
Table 1. Legionnaires Disease: Six Clinical Predictors and Diagnostic Eliminators in Adults Admitted with Pneumonia a
Diagnostic Predictors Diagnostic Eliminators
Clinical Predictors
  • Fever (>102°F)
Clinical Eliminators
  • Sore throat
  • Severe myalgias
Laboratory Predictors b
  • Highly elevated ESR (>90 mm/h) or CRP (>180 mg/L)
  • Highly elevated ferritin levels (>2 X normal)
  • Hypophosphatemia (on admission/early)
  • Highly elevated CPK (>2 X normal)
  • Microscopic hematuria (on admission)
Laboratory Eliminators
  • Leukopenia
  • Thrombocytopenia
  • Negative chest radiographic findings (no infiltrates)
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.



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