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 for culture and urine for 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 overnight within 14 days before symptom onset)
• Hospitalized patients with healthcare-associated pneumonia (pneumonia with onset ≥48 hours after admission) at risk for Legionnaires’ disease
• Patients with an overnight stay in a healthcare facility within 14 days before symptom onset
• Patients with an epidemiologic link to a setting with a confirmed source of Legionella or that has been associated with at least one laboratory-confirmed case of Legionnaires’ disease

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

• Other patients with healthcare-associated Legionnaires’ disease diagnosed in the past 12 months
• Positive environmental tests for Legionella
• 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

Timely reporting of healthcare-associated cases ensures that steps can be taken to protect these highly susceptible populations.

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 10–15% of all reported cases of Legionnaires’ disease occur in people who have traveled during their exposure period. Outbreaks among travelers can be difficult to detect because of

• The low attack rate
• The time interval between exposure and symptom onset
• Dispersal of people from the source of the outbreak
• Underdiagnosis of cases

Therefore, collecting and reporting information about overnight travel is important. See “Reporting” below for information about reporting cases, including travel information.

See Healthcare Investigation Resources for more information about healthcare exposures.

Preferred Diagnostic Tests

Culture

Isolation of Legionella on media that supports growth of Legionella (i.e., Buffered Charcoal Yeast Extract [BCYE] agar) is confirmatory and an important method for diagnosis. Isolation of Legionella can come from lower respiratory secretions, lung tissue, pleural fluid, or a normally sterile site. Culturing specimens can detect Legionella species and serogroups that the urinary antigen test does not.

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

Note that laboratories sometimes reject lower respiratory specimens during a work-up for pneumonia based on specimen quality (e.g., due to lack of white blood cells in the sample, contamination with other bacteria). However, laboratories should not reject lower respiratory specimens for these reasons when working-up Legionnaires’ disease because Legionella can often be recovered.

• Sputum produced by patients with Legionnaires’ disease may not have many white blood cells.³
• Contaminating bacteria do not negatively impact isolation of Legionella on selective media (e.g., Buffered Charcoal Yeast Extract [BCYE] agar plus antibiotics).⁴

Urinary Antigen Test

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

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.

¹ Cross reactions with other species and serogroups have been documented.
²Avni T, Bieber A, Green H, et al. Diagnostic accuracy of PCR alone and compared to urinary antigen testing for detection of Legionella spp.: A systematic review. J Clin Micro. 2016;54(2):401–11.
³CDC labs do not perform serologic testing for legionellosis diagnosis due to inherent challenges in obtaining appropriate specimens. It is important to note that because paired sera are required, results are delayed and thus may not be useful for acute case diagnosis or during active outbreak investigations.

Advantages and Disadvantages for Each Diagnostic Test

¹ Cross reactions with other species and serogroups have been documented.
² Yu V, Plouffe JF, Pastoris MC, et al. Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: An international collaborative survey. J Infect Dis. 2002;186:127–8.
³ Laboratories can develop, adopt, or use existing assays (known as laboratory developed tests) for in vitro diagnostic purposes. Labs do this by establishing and validating test performance under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) requirements or equivalent regulations.
⁴ Currently the U.S. Food and Drug Administration has cleared at least one nucleic acid-based molecular assay for Legionella pneumophila detection
⁵ CDC labs do not perform serologic testing for legionellosis diagnosis due to inherent challenges in obtaining appropriate specimens. It is important to note that because paired sera are required, results are delayed and thus may not be useful for acute case diagnosis or during active outbreak investigations.
⁶ McDade JE, Shepard CC, Fraser DW, Tsai TR, Redus MA, Dowdle WR. Legionnaires’ disease: isolation of a bacterium and demonstration of its role in other respiratory disease. N Engl J Med. 1977;297(22):1197-1203.

Treatment

If your patient has Legionnaires’ disease, please see the most recent IDSA-ATS guidelines for treatment of community-acquired pneumonia and the most recent IDSA-ATS guidelines for treatment of hospital-acquired pneumonia. Note that first line treatment, however, does not always include Legionella-directed antibiotics (e.g., macrolides and respiratory fluoroquinolones). While it is preferred that you obtain diagnostic testing 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.

Prevention

Minimizing Legionella growth in complex building water systems and devices is key to preventing infection. Timely identification and reporting of legionellosis cases are also important because this allows public health officials to act quickly. This way they can identify and stop potential clusters and outbreaks by linking new cases to previously reported ones.

Reporting

Report cases and outbreaks of Legionnaires’ disease to your local, state, or territorial health department. Refer to your state or territorial health department website to find more information about how to contact your state, territorial, or local health department.