Diagnosis, Treatment, and Prevention

The preferred diagnostic tests for Legionnaires’ disease are culture of lower respiratory secretions (e.g., sputum, bronchoalveolar lavage) on selective media and the Legionella urinary antigen test. Serological assays can be nonspecific and are not recommended in most situations. Best practice is to obtain both sputum culture and the urinary antigen test concurrently. Sputum should ideally be obtained prior to antibiotic administration, but antibiotic treatment should not be delayed to facilitate this process. The urinary antigen test can detect Legionella infections in some cases for days to weeks after treatment.

 

Indications for Legionnaires’ Disease Testing

Listed below are indications that warrant testing patients with pneumonia for Legionnaires’ disease:

• Patients who have failed outpatient antibiotic treatment for community-acquired pneumonia
• Patients with severe pneumonia, in particular those requiring intensive care
• Immunocompromised patients with pneumonia*
• Patients with a travel history (patients who have traveled away from their home within 10 days before the onset of illness)

  The Council of State and Territorial Epidemiologists (CSTE) position statement outlines case definitions for confirmed and suspected legionellosis. Read the position statement.

• All patients with pneumonia in the setting of a Legionnaires’ disease outbreak
• Patients at risk for Legionnaires’ disease with healthcare-associated pneumonia (pneumonia with onset ≥ 48¹ hours after admission)

*May also consider testing for Legionnaires’ disease in patients with other risk factors for Legionnaires’ disease as listed here: https://www.cdc.gov/legionella/clinicians/disease-specifics.html

Testing for healthcare-associated Legionnaires’ disease is especially important if any of the following are identified in a health care facility:

• Other patients with healthcare-associated Legionnaires’ disease diagnosed in the past 12 months
• Positive environmental tests for Legionella in the past 2 months
• Current changes in water quality that may lead to Legionella growth (such as low chlorine levels or nearby construction)

 

Importance of Asking about Travel and Healthcare Exposures

The majority of recognized Legionnaires’ disease outbreaks are associated with travel (hotels, resorts, cruise ships) or healthcare settings (hospitals, long-term care facilities)² . Approximately 10% of all reported cases of Legionnaires’ disease occur in people who have traveled during the 10 days before symptom onset. Outbreaks among travelers can be difficult to detect because of the low attack rate, long incubation period, and the dispersal of persons from the source of the outbreak, so collecting and reporting information about overnight travel is important.

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Preferred Diagnostic Tests

Culture

Isolation of Legionella on selective media (i.e., Buffered Charcoal Yeast Extract [BYCE] agar) from lower respiratory secretions, lung tissue, pleural fluid, or a normally sterile site is confirmatory and an important method for diagnosis. In addition, if urinary antigen testing is negative but Legionnaires’ disease is still suspected, a respiratory culture should be conducted to look for other Legionella species and serogroups that the urinary antigen test does not detect.

Comparing clinical and environmental isolates using serological and molecular techniques can help identify the source in Legionnaires’ disease outbreak investigations. Because Legionella is commonly found in the environment, clinical isolates can help interpret the findings of an environmental investigation.

Urinary Antigen Test

The most commonly used laboratory test for diagnosis of legionellosis is the urinary antigen test, which detects a molecule of the Legionella bacterium in urine. If the patient has pneumonia and the test is positive, then the patient is considered to have Legionnaires’ disease. The test can remain positive for a few weeks after infection, even with antibiotic treatment. The urinary antigen test detects the most common cause of legionellosis, L. pneumophila serogroup 1. However, all species and serogroups of legionellae are potentially pathogenic, so a patient with a negative urinary antigen result could have legionellosis caused by other Legionella species and serogroups.

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Sensitivity and Specificity of Diagnostic Tests

Sensitivity varies depending on the quality and timing of clinical specimen collection, as well as technical skill of the laboratory worker performing the test. The table below provides general ranges for the sensitivity and specificity of each diagnostic test.

Test	Sensitivity (%)	Specificity (%)
Culture	20–80	100
Urinary antigen for L. pneumophila serogroup 1* (Lp1)	70–100	95–100
Paired serology**	80–90	>99
Direct Fluorescent Antibody (DFA) Stain	25–75	≥95
Polymerase Chain Reaction (PCR)	unknown	unknown

*Cross reactions with other species and serogroups have been documented.

**CDC labs do not perform serology testing for legionellosis diagnosis due to inherent limitations of this approach.

 

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Other Advantages and Disadvantages for Each Diagnostic Test

Test	Advantages	Disadvantages
Culture	Detects all species and serogroups Clinical and environmental isolates can be compared	Technically difficult Slow (>5 days to grow) Sensitivity highly dependent on technical skill Affected by appropriate antibiotic treatment Requires BCYE agar, which some laboratories may not have readily available
Urinary Antigen	Rapid (same day)	Can only be used to identify L. pneumophila serogroup 1* (Lp1) [which may account for up to 80% of cases] Does not allow for molecular comparison to environmental isolates
Serology**	Possible to detect species and serogroups other than Lp1	Must have paired sera collected at acute onset to 2 weeks after symptoms and 3 to 6 weeks later Approximately 5 to 10% of the population has titer 1:≥256 (single acute phase antibody titers of 1: ≥256 do not discriminate between cases of Legionnaires’ disease and other causes of community-acquired pneumonia)
DFA	Can be performed on pathologic specimens (usually lung tissue) Possible to detect species and serogroups other than Lp1	Technically difficult
PCR	Can be performed on pathologic specimens (usually lung tissue) Rapid Possible to detect species and serogroups other than Lp1	Assays vary by laboratory and are not FDA-approved

*Cross reactions with other species and serogroups have been documented.

**CDC labs do not perform serology testing for legionellosis diagnosis due to inherent limitations of this approach.

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Treatment

If your patient has Legionnaires’ disease, please see the most recent IDSA-ATS guidelines for treatment of community-acquired pneumonia [46 pages] and the most recent IDSA-ATS guidelines for treatment of hospital-acquired pneumonia [51 pages]. Note that first line treatment, however, does not always include Legionella-directed antibiotics (e.g., macrolides and respiratory fluoroquinolones). While it is preferred that diagnostic testing be obtained before antibiotic administration, antibiotic treatment should not be delayed to facilitate this process.

If your patient has Pontiac fever, antibiotic treatment should not be prescribed. It is a self-limited illness that does not benefit from antibiotic treatment. Patients usually recover within 1 week.

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Prevention

Minimizing Legionella growth in complex building water systems and devices, including potable water, hot tubs, decorative fountains, and cooling towers, is key to preventing infection. Timely identification and reporting of legionellosis cases is also important because this allows public health officials to quickly identify and stop potential clusters and outbreaks by linking new cases to previously reported ones.

 

References

• Benin AL, Benson RF, Besser RE. Trends in Legionnaires disease, 1980–1998: declining mortality and new patterns of diagnosis. Clin Infect Dis. 2002;35(9):1039–46.
• Garrison LE, Kunz JM, Cooley LA, et al. Vital Signs: Deficiencies in environmental control identified in outbreaks of Legionnaires’ disease — North America, 2000–2014. MMWR Morb Mortal Wkly Rep. 2016;65:576–84.
• Hicks LA, Garrison LE, Nelson GE, et al. Legionellosis—United States, 2000–2009. MMWR Morb Mortal Wkly Rep. 2011;60(32):1083–6.
• Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61–111.
• Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society concensus guidelines on the management of community-acquired pneumonia. Clin Infect Dis. 2007;44:S27–72.
• Smith P, Moore M, Alexander N, et al. Surveillance for travel-associated legionnaires disease—United States, 2005–2006. MMWR Morb Mortal Wkly Rep. 2007;56(48):1261–3.

 

Footnotes

1.  Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61–111
2. Garrison LE, Kunz JM, Cooley LA, et al. Vital Signs: Deficiencies in Environmental Control Identified in Outbreaks of Legionnaires’ Disease — North America, 2000–2014. MMWR Morb Mortal Wkly Rep. 2016;65:576 – 584. DOI: http://dx.doi.org/10.15585/mmwr.mm6522e1