New Diagnositics for Legionella Pneumonia May Streamline Care Continuum

Legionella species are gram-negative bacteria found in natural fresh water and soil; however, the bacteria are usually not present in adequate amounts to cause disease in individuals unless amplified and aerosolized in manmade water or cooling systems.^1-3 In human-formed water systems, such as hot tubs, plumbing, fountains, cooling towers that use centralized air-cooling systems, and shower heads, Legionella can proliferate and become transmissible to susceptible individuals through aerosolization, with Legionella pneumophila causing the majority of disease and serogroup 1 as the most commonly detected.⁴

When Legionella bacteria cause disease, the subsequent manifestations are called legionellosis, which encompasses Legionnaires’ disease, Pontiac fever, and other extrapulmonary Legionella infections.⁴ Pontiac fever is most often a self-limiting, short-duration, flulike illness,² whereas Legionnaires’ disease commonly presents as a severe pneumonia.⁵ The majority of legionellosis syndromes reported are Legionnaires’ disease caused by Legionella pneumophila, with cases increasing steadily since the early 2000s.⁶ Preventing Legionnaires’ disease requires decreasing the risk of bacterial growth and transmission by utilizing water management systems to control Legionella and prevent outbreaks.¹

Rapid detection of Legionella infections in susceptible patients is crucial for public health officials to identify water sources and prevent outbreaks and for providing proper treatment to the patient.² The increase in reported legionellosis cases in the United States may be due to heightened detection methods, increased reporting and surveillance, and an aging population with increasing chronic medical conditions.²

Certain adults are more susceptible to legionellosis, including individuals 50 years and older and those with certain medical histories, including chronic lung disease, immune system disorders, past or current smoking, systemic malignancies, and underlying illnesses such as diabetes, renal failure, and hepatic failure.⁷ Current data on Legionella pneumonia are limited due to studies on older cohorts, outbreaks, and surveillances that lack detailed clinical characteristics of the study participants.⁸

Additionally, the population at risk for Legionella infections has evolved to include individuals with advanced age, comorbidities, and immune dysfunction.8 Approximately 2% to 9% of community-acquired pneumonia in hospitalized patients is caused by Legionella species.⁸ Morbidity and mortality of Legionnaires’ disease is high, with an overall mortality rate of 4% to 18%, and may surpass 20% to 30% in patients with comorbidities or those requiring intensive care.^3,8 Additionally, Legionnaires’ disease is the second most expensive waterborne disease reported in the United States, with hospital stays totaling more than $145,000 in direct health care costs, indicating a significant economic burden.³

As Legionella pneumonia is often underrecognized and underdiagnosed despite rising case numbers, clinician awareness and timely diagnosis are essential to identifying cases so public health officials can contain outbreaks.⁷ Specific diagnostic tests, including cultures or molecular testing of lower respiratory secretions, can detect different Legionella species, coupled with a Legionella urinary antigen test for Legionella pneumophila serogroup 1.⁷ According to the Centers for Disease Control and Prevention (CDC), positive Legionella tests must be reported to public health authorities and local health departments to identify the source, prevent outbreaks, and utilize surveillance systems to collect data for investigation.⁴

Testing for Legionnaires’ disease associated with health care systems may be indicated under certain circumstances at an individual facility, which can be identified by individual infection control staff.⁷ Guidance from the CDC and the Infectious Diseases Society of America (IDSA) currently suggests Legionella urinary antigen testing, coupled with a culture of lower respiratory secretions on selective media, or a molecular test of respiratory secretions to detect Legionella.^7,9 Legionella is an “atypical” organism, and it is not detectable on Gram stain or cultivatable on standard bacteriologic media; therefore testing should be specifically requested in the microbiology laboratory, and treatment should include antibiotics that cover atypical organisms.^3,10 Of note, the Legionella urinary antigen test only detects Legionella pneumophila serogroup 1.⁷ The sensitivity and specificity of each test can vary based on the quality of the sample and the skill of the medical professional performing the test.

The Legionella urinary antigen test is quick, with a sensitivity of 20% to 80% and specificity of 100%, and can often be detected in urine for days to weeks after treatment.¹¹ Results may be available up to 4 hours after sample collection.² Polymerase chain reaction (PCR) tests are also rapid, with results typically available within 1 to 48 hours after specimen collection, and with a sensitivity of 95% to 99% and a specificity of greater than 99%; however, availability may be limited and costly based on the specific institution.^2,11 Cultures of lower respiratory samples are 20% to 80% sensitive and 100% specific, but require specialized media to test for Legionella species and may take up to 14 days to grow.¹¹

The most common antibiotics used to treat Legionnaires’ disease are respiratory fluoroquinolones and macrolides.^7,9,10 Current IDSA guidelines do not favor fluoroquinolones (levofloxacin, moxifloxacin) over macrolides (azithromycin, clarithromycin)⁹; however, patient-specific factors, such as drug interactions and concomitant disease states, should be taken into consideration when choosing an agent. A systematic review and meta-analysis comparing the effectiveness of fluoroquinolones with macrolides for treatment of Legionella pneumonia indicated no difference in clinical cure rates, effectiveness, or reduction of mortality in patients with Legionella pneumonia.¹² Despite the increase in prevalence, there is a lack of current data on the clinical phenotype, diagnostic patterns, and outcomes in individuals with Legionella pneumonia.⁸

A recent cohort study published in 2026 examined the modern-day clinical course and outcomes of adults with lab-confirmed Legionella pneumonia.⁸ This retrospective, multicenter cohort study included 344 patients with laboratoryconfirmed Legionella defined by a positive urinary Legionella antigen test, a positive Legionella PCR from respiratory specimens, or a positive Legionella culture from respiratory specimens.⁸

The primary outcome was 30-day all-cause mortality from the date of Legionella diagnosis, with secondary outcomes of severe disease described as requiring high-flow nasal cannula, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation anytime while hospitalized.⁸ Legionella species were identified by urinary antigen in 51.5% of cases, PCR of respiratory specimens in 52.9%, and culture in 25% of cases.⁸ In patients with Legionella identified by culture or PCR who also had a urinary antigen test ordered, only 25.6% of those urine tests resulted as positive.⁸

This study underscores the importance of coupled testing, emphasizing the high sensitivity of PCR to detect Legionella.⁸ The diagnostic patterns in this cohort indicated that relying on urinary antigen or respiratory culture alone would have failed to identify 28.5% of cases, and no single diagnostic method is sufficient.⁸ Of note, 45.1% of the cohort was immunocompromised and had higher odds of 30-day mortality.⁸ Cirrhosis was also associated with increased odds of mortality.⁸ More than 94% of patients required hospitalization, with more than 33% admitted to the intensive care unit (ICU) and nearly 25% requiring mechanical ventilation.⁸ Mortality of individuals admitted to the ICU was 25%, which is consistent with other studies of critically ill patients.⁸ Levofloxacin (48.6%) was more commonly prescribed than azithromycin (36.9%), and the median duration of antibiotics was 10 days among survivors.⁸ Age, immunocompromised status, and lymphopenia on presentation were associated with an increased risk of adverse outcomes.⁸

This cohort demonstrated that Legionella pneumonia was associated with substantial short-term mortality, with the results providing valuable insight into the modern-day outcomes and diagnostics in these patients.8 This study identifies Legionella pneumonia as a substantial burden of clinical illness with outcomes similar to those observed in other studies.

The 30-day mortality rate in this study was 11.9%, with ICU admission required in 36.1% of hospitalized patients.⁸ These results are similar to those reported in a study by Serrano et al, which demonstrated 30-day mortality rates of 6.2% and in which 24.2% required ICU admission.¹³ The results also mimic previous studies demonstrating ICU admissions ranging from 20% to 27%, with overall mortality rates of 4% to 18%.³ An increase in reported Legionella infections in the US over the past decade highlights the importance of early, rapid diagnosis, especially among severely ill patients and during potential outbreaks.9 The study by Pulsipher et al underscores the need to utilize and comprehend coupled diagnostic testing, as a significant amount of infections may have been missed if relying on a single diagnostic modality.⁸ Antibiotics targeting Legionella species should be included in empiric therapy for severe community-acquired pneumonia, as insufficient or delayed therapy has been associated with worse prognosis in patients.³ Legionellosis is becoming an important public health threat, with increases in incidence and health care costs associated with the disease.³

References

1. About Legionnaires’ disease. CDC. August 6, 2025. Accessed April 14, 2026. https://www.cdc.gov/legionella/about/

2. Mercante JW, Winchell JM. Current and emerging Legionella diagnostics for laboratory and outbreak investigations. Clin Microbiol Rev. 2015;28(1):95-133. doi:10.1128/CMR.00029-14

3. Viasus D, Gaia V, Manzur-Barbur C, Carratalà J. Legionnaires’ disease: update on diagnosis and treatment. Infect Dis Ther. 2022;11(3):973-986. doi:10.1007/s40121-022-00635-7

4. Clinical overview of Legionnaires’ disease. CDC. June 9, 2025. Accessed April 14, 2026. https://www.cdc.gov/legionella/hcp/clinical-overview/index.html

5. Clinical features of Legionnaires’ disease and Pontiac fever. CDC. June 9, 2025. Accessed April 28, 2026. https://www.cdc.gov/legionella/hcp/clinical-signs/index.html

6. Surveillance report 2020-2021. CDC. December 9, 2025. Accessed April 27, 2026. https://www.cdc.gov/legionella/php/surveillance/surveillance-report-2020-2021.html

7. What clinicians need to know about Legionnaires’ disease. CDC. Accessed April 27, 2026. https://www.cdc.gov/legionella/downloads/fs-legionella-clinicians.pdf

8. Pulsipher AM, Khattar G, VanDolah H, et al. Legionella pneumonia in the modern era: clinical features and predictors of mortality. Clin Infect Dis. Published online February 21, 2026. doi:10.1093/cid/ciag085

9. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi:10.1164/rccm.201908-1581ST

10. Mandell LA, Wunderink RG, Anzueto A, 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;44(Suppl 2):S27-S72. doi:10.1086/511159

11. Laboratory testing for Legionella. CDC. June 9, 2025. Accessed May 5, 2026. https://www.cdc.gov/legionella/php/laboratories/index.html

12. Jasper AS, Musuuza JS, Tischendorf JS, et al. Are fluoroquinolones or macrolides better for treating Legionella pneumonia? a systematic review and meta-analysis. Clin Infect Dis. 2021;72(11):1979-1989. doi:10.1093/cid/ciaa441

13. Serrano L, Ruiz LA, Perez-Fernandez S, et al. Short- and long-term prognosis of patients with community-acquired Legionella or pneumococcal pneumonia diagnosed by urinary antigen testing. Int J Infect Dis. 2023;134:106-13. doi:10.1016/j.ijid.2023.05.065