Legionnaires' disease

Legionnaires' disease is a type of legionellosis that manifests with atypical pneumonia (shortness of breath, cough), typically in combination with gastrointestinal (e.g., diarrhea) and neurological (e.g., confusion) symptoms. The condition is typically caused by Legionella pneumophila, a gram-negative rod that thrives in warm aqueous environments such as drinking-water systems, hot tubs, and air-conditioning units. Transmission occurs via inhalation of contaminated aerosolized water droplets; disease outbreaks are common. Laboratory abnormalities are common, especially hyponatremia. Diagnosis can be confirmed using a urine antigen test, PCR, or microbiological studies. Fluoroquinolones or macrolides are the treatment of choice. Legionellosis is a notifiable disease in the US, and steps should be taken to eliminate contaminated sources and prevent outbreaks.

Pontiac fever is a more mild, flu-like type of legionellosis that is self-limiting.

• Legionellosis: an infection caused by Legionella spp.
• Legionnaires' disease: a type of legionellosis that manifests as atypical pneumonia
• Pontiac fever: a type of legionellosis that manifests with flu-like symptoms without pneumonia

• Manifests almost exclusively in adults ^[1]
• Outbreaks are typical. ^[2]
• Locations at increased risk of a legionella outbreak include: ^[1]
  • Nursing homes
  • Hospitals
  • Confined travel accommodations (e.g., cruise ships, hotels, resorts) ^[2]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogens ^[2]
  • Legionella pneumophila
    • A gram-negative, aerobic, facultative intracellular bacterium
    • Causes ∼ 90% of legionellosis ^[3]
  • Other Legionella spp. (e.g., L. micdadei, L. longbeachae)
• Transmission ^[3]
  • Inhalation of contaminated aerosols
    • Cold and hot water systems
    • Whirlpools/hot tubs, swimming pools, showers
    • Air conditioning systems with contaminated condensed water
  • Person-to-person transmission is uncommon.
• High-risk groups ^[1]
  • Individuals ≥ 50 years of age
  • Individuals with certain chronic diseases (e.g., COPD, diabetes mellitus, CKD)
  • Immunocompromised individuals
  • Smokers (current or former)

• Incubation period: 2–10 days
• Fever, chills, headache
• Severe atypical pneumonia: dry cough which can become productive, shortness of breath, bilateral crackles
• Relative bradycardia
• Diarrhea
• Neurological features, especially confusion, agitation, and stupor

Legionnaires' disease should always be considered in patients with signs of atypical pneumonia and diarrhea in combination with possible exposure (e.g., cruise ship travel, use of a whirlpool).

Pontiac fever ^[3]

• Mild course of legionellosis without pneumonia
• Characterized by flu-like symptoms (e.g., fever, headache, myalgia)
• Incubation period: 1–2 days ^[3]
• Self-limiting disease; specific treatment is not needed.

Extrapulmonary legionellosis ^[3]

Extrapulmonary legionellosis has various possible manifestations, e.g.:

• Skin and soft tissue infection
• Septic arthritis
• Endocarditis

Extrapulmonary legionellosis is rare and most commonly affects immunosuppressed patients.

Approach ^[2][4]

• Obtain routine studies and confirm a diagnosis of pneumonia.
• Consider Legionnaires' disease in patients with:
  • Epidemiological and/or individual risk factors (see “Epidemiology” and “Etiology”)
  • Severe community-acquired pneumonia (CAP), e.g., according to IDSA/ATS criteria for severe CAP
• Confirm diagnosis using a legionella urine antigen test, PCR, and/or culture.

Routine pneumonia diagnostics may show nonspecific but supportive findings.

Routine studies

Laboratory studies ^[2][5]

• CBC
  • Leukocytosis
  • Thrombocytopenia
• Serum studies
  • Hyponatremia
  • Hypophosphatemia
  • ↑ Creatinine
  • ↑ Transaminases ^[5]
  • ↑ CRP
  • ↑ Ferritin
  • ↑ Procalcitonin
• Urine studies
  • Microscopic hematuria
  • Proteinuria

Hyponatremia may be caused by SIADH or by dilution and is more commonly associated with Legionnaires' disease than with other causes of pneumonia. ^[2][5]

Imaging ^[5][6]

• Chest x-ray
  • Nonspecific findings
  • Findings often include either: ^[2]
    • Lobar pneumonia (with or without pleural effusion) and lobar pulmonary consolidations
    • Diffuse reticular opacities
• Chest CT; findings may include:
  • Unilateral or bilateral pulmonary consolidations
  • Ground-glass opacities
  • Pleural effusion

Confirmatory studies ^[2][7]

• Legionella urinary antigen test ^[2]
  • Most important diagnostic tool
  • High specificity, high sensitivity, fast (results available within 15 minutes) ^[2]
  • Can only detect Legionella pneumophila serogroup 1 antigens ^[2]
• PCR
  • High specificity, high sensitivity, fast (results typically available within hours)
  • Preferred specimens: sputum, bronchoalveolar lavage (BAL) fluid
• Microbiological studies
  • Legionella culture (gold standard) ^[7]
    • Requires buffered charcoal yeast extract agar with iron and cysteine ^[5]
    • Slow (results typically after 3–5 days) ^[7]
    • High specificity, moderate to low sensitivity depending on specimen
    • Preferred specimens: sputum, BAL fluid
  • Sample stains
    • Gram stain of respiratory secretions typically shows many neutrophils but no organisms. ^[3]
    • Visualization of Legionella requires silver stain. ^[5]
• Serology
  • Not routinely used
  • A four-fold rise in antibody titer confirms legionellosis.

General principles ^[2]

• Legionellosis is a notifiable disease. ^[8]
• Early antibiotic therapy is the mainstay of treatment.
• Affected individuals do not need to isolate because person-to-person transmission is uncommon.
• Offer supportive therapy for pneumonia as needed.
• See “Management of pneumonia” for further details, including criteria for ICU admission.

Legionnaires' disease has a mortality rate of ∼10% in patients without high-risk factors. ^[1][2]

Antibiotic therapy ^[2][4]

• Empiric antibiotics for pneumonia
  • Initiate as soon as possible.
  • Choose initial agents based on the clinical setting.
    • See “Empiric antibiotics for hospital-acquired pneumonia.”
    • See “Empiric antibiotics for community-acquired pneumonia.”
  • Empiric regimens for patients hospitalized with CAP typically include coverage for Legionella (e.g., macrolides, fluoroquinolones, or doxycycline).
• Targeted antibiotics
  • Once Legionnaires' disease is confirmed, initiate treatment with or switch to one of the following agents:
    • Fluoroquinolones (preferred): e.g., levofloxacin ^[2]
    • Macrolides: e.g., PO azithromycin , or IV azithromycin
    • Alternative agents include tigecycline and doxycycline ^[2][5]
  • Initial parenteral treatment is recommended for hospitalized patients.

Empiric treatment of atypical pneumonia and antibiotic regimens for inpatient treatment of CAP need to cover Legionella species.

Course of action when contaminated water sources are detected in medical facilities:

• Contaminated water systems should be disinfected.
• Use terminal tap water filters, especially for high-risk patients (e.g., immunocompromised individuals, older adults).

References:^[9]