Legionnaires Disease Workup

  • Author: Burke A Cunha, MD; Chief Editor: Michael Stuart Bronze, MD   more...
 
Updated: Nov 15, 2011
 

Laboratory Studies

  • While pneumonias caused by numerous pathogens share similar laboratory findings, hyponatremia (sodium < 130 mEq/L) secondary to the syndrome of inappropriate antidiuretic hormone is more common in legionnaires disease (LD) than in pneumonias secondary to other pathogens; however, this is not specific for LD.
  • Non-specific laboratory findings in LD include the following:
    • Elevated liver enzyme levels
    • Highly elevated ESR
    • Hihgly elevated ferritin levels
    • Increased C-reactive protein levels (>30 mg/L)
    • Hypophosphatemia (specific to LD excluding other causes of hypophosphatemia)[6]
    • Microscopic hematuria
    • Proteinuria (40%)
  • Gram stain
    • Typically, many leukocytes and a paucity of organisms are observed.
    • If visible, the organisms are small, faintly staining, gram-negative bacilli.
  • 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.
    • Legionella requires buffered 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 has a lower sensitivity. 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). 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 test
    • 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).[7]
    • The advantages of this test 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.[7]
    • The urinary antigen result can remain positive for months after the acute episode has resolved.[7]
  • Amplification with polymerase chain reaction
    • Polymerase chain reaction (PCR) 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

  • No typical LD radiographic presentation exists.[8]
  • Rapidly progressive asymmetrical infiltrates are characteristic of LD.
  • Approximately one quarter of patients had infiltrates that were described as interstitial. Almost half of the patients had patchy alveolar infiltrates.
  • In general, the abnormalities are typically unilateral and are found in the lower lobes.
  • Pleural effusions are found in one third of patients.
  • Cavity and abscess formation are rare and can occur in immunocompromised hosts.
  • Improvement revealed on the chest radiograph can lag behind the clinical improvement by 5-7 days. The abnormalities on chest radiograph can take up to 3-4 months to resolve completely.
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Procedures

  • Bronchoscopy: While the sensitivity of specimens retrieved via bronchoscopy is comparable to that of sputum, BAL fluid gives a higher yield than bronchial wash specimens.
  • Thoracentesis: If a pleural effusion is present, fluid can be evaluated using DFA or LD culture.
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Histologic Findings

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

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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, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

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

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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

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.

Eleftherios Mylonakis, MD  Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital

Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD  Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center

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

Disclosure: Nothing to disclose.

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Table. Modified Winthrop-University Hospital Infection Disease Division's Point System for Diagnosing Legionnaires Disease in Adults
Clinical Features Qualifying Conditions Point Score
Temperature >103°F*With relative bradycardia+5
HeadacheAcute onset+2
Mental confusion/lethargy*Not drug induced+4
Ear painAcute onset-3
Nonexudative pharyngitisAcute onset-3
HoarsenessAcute, not chronic-3
Sputum (purulent)Excluding chronic bronchitis-3
Hemoptysis*Mild/moderate-3
Chest pain (pleuritic)Rapidly progressive asymmetrical



infiltrates* (excluding severe influenza/severe acute respiratory syndrome)



-3
Loose stools/watery diarrhea*Not drug induced+3
Abdominal pain*With or without diarrhea+5
Renal failure*Acute, not chronic+3
Shock/hypotension*Not 2° to acute cardiac-5
/pulmonary causes+5
SplenomegalyExcluding non-CAP causes-5
Lack of response to beta lactamsAfter 72 h (excluding viral pneumonias)+5
Laboratory Features
Chest radiographRapidly progressive asymmetrical infiltrates*



(excluding severe influenza/SARS)



+3
↓ PO2 with ↑ A-a gradient (>35)*(Excluding severe influenza/SARS)-5
↓ Na+Acute onset+1
↓ PO4 =*Acute onset+5
↑ SGOT/SGPT (early mild/transient)*Acute onset+4
↑ Total bilirubinOtherwise unexplained+1
↑ LDH (>400 U/L)*Excluding HIV/PCP-5
↑ CPK/aldolaseOtherwise unexplained+4
↑ CRP (>30 mg/L)Acute onset+5
↑ Cold agglutinins (≥ 1:64)Acute onset-5
↑ CreatinineAcute onset+2
Microscopic hematuria*Excluding trauma, BPH, Foley catheter,



bladder/renal neoplasms



+2
Likelihood of Legionella infection
Total points>15 Legionella infection very likely
5-15 Legionella infection likely
< 5 Legionella infection unlikely
*Otherwise unexplained (acute and associated with pneumonia)
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