Legionella pneumophila

Indications for Testing

Community-acquired pneumonia with gastrointestinal symptoms
Consider testing if nosocomial pneumonia occurs or if other known Legionella pneumonia is present in hospital

Laboratory Testing

Legionellosis resources (CDC)
Perform routine microbiology testing only for pathogens that would alter empirical decisions (recommendation from Infectious Diseases Society of America and American Thoracic Society)
Nonspecific testing
- Serum sodium – hyponatremia
- Serum phosphate – hypophosphatemia
- Urine analysis – hematuria
- CBC – thrombocytopenia common
- Liver function studies – elevated transaminases
Consider testing for other common agents of community-acquired pneumonia – Streptococcus pneumoniae, Chlamydophila pneumoniae, Mycoplasma pneumoniae
Rapid testing may aid in early initiation of treatment
- Point of care testing – available for urine specimens (sensitivity 70-80%; specificity 97-100%)
- Urine antigen testing (EIA)
  - Urine antigen testing more sensitive than DFA and highly specific for serogroup 1
  - Detects only serogroup 1 (most common serogroup causing disease)
  - Antigens or antibodies may be detected as early as 1 day after symptom onset; positivity of test may persist >60 days
- DFA of respiratory specimen
  - Highly insensitive compared to PCR and culture
  - Can detect various serogroups
  - Technically demanding; requires large respiratory specimen
  - Urine antigen detects serogroup 1; DFA detects various serogroups
- PCR testing of respiratory secretions – good sensitivity; rate of false positives is 5-10%
Culture – considered gold standard in diagnosis
- Best yield from sputum, which may be difficult to obtain with legionellosis
- May be used to confirm PCR results
- Takes at least 48 hours
- Genotyping isolates may help identify source of outbreak
Serological testing may be used for retrospective diagnosis
- Seroconversion may take several weeks

Imaging Studies

Chest x-ray
- Rapidly progressive asymmetrical infiltrates are common
- Infiltrates may initially enlarge concurrent with clinical improvement while on appropriate antimicrobial therapy

Differential Diagnosis

Pneumonia
- Other atypical pneumonia (eg, mycoplasma)
- Bacterial pneumonia (eg, S. pneumoniae)
- Viral pneumonia (eg, influenza, parainfluenza, hantavirus)
- Zoonotic pneumonias (Coxiella burnetii, C. pneumoniae and psittaci, Francisella tularensis)
Gastrointestinal
- Influenza
- Diarrhea (viral, bacterial, parasitic)

Legionellosis refers to two clinical syndromes caused by bacteria of the genus Legionella – Legionnaires’ disease and Pontiac fever. Legionnaires’ disease is considered an atypical pneumonia.

Epidemiology

Incidence – >10,000 annually in U.S.
- May be responsible for 3-8% of all community-acquired pneumonia
Age – usually 45-64 years; rare cause of pneumonia in children
Sex – M>F; 2-3:1
Transmission
- Mostly sporadic cases
- More common in summer months – outbreaks of pneumonia have occurred after inhalation of contaminated water droplets from water sources such as evaporative coolers, hot tubs, heating systems
- Person-to-person transmission has not been shown
- Nosocomial cases are not uncommon
  - Sources of infection are often hospital showers, drinking fountains, and respiratory-therapy equipment

Organism

Legionella is a fastidious gram-negative coccobacillus
- Widespread in nature but live mainly in freshwater bodies
- Parasitizes freshwater amoeba in the environment and pulmonary macrophages in humans
>50 species compose at least 70 different serogroups of Legionellae
L. pneumophila is major pathogen and most commonly encountered member of group
- Serogroup 1 is most common infecting type

Risk Factors

Adults
- Older age (average ~55 years)
- Cigarette smoking
- Underlying chronic disease (eg, chronic obstructive pulmonary disease, diabetes, renal failure)
- Compromised immune system (immunosuppressive therapy or T-cell dysfunction, including cancer)
- Recent surgery
- Alcoholism
- Long-term use of breathing machines (ventilators)
Children – prematurity, immunocompromised, bronchopulmonary dysplasia

Clinical Presentation

Legionnaires' disease
- Incubation period of 2-15 days
  - Prodromal phase of headache and myalgia progressing to fever with chills
  - Productive cough, possibly with hemoptysis
  - Chest pain
  - Shortness of breath
- Symptoms may suggest pneumococcal pneumonia
- Frequently includes gastrointestinal symptoms – primarily loose stools, diarrhea and/or abdominal pain
- Frequently associated systemic involvement – kidney, liver and central nervous system dysfunction
  - Central nervous system – headache, lethargy, confusion, ataxia, encephalopathy
- Case fatality rate – 5-30%
  - Greater risk of death exists for elderly and immunocompromised
Pontiac fever
- Self-limiting, febrile illness with non-pneumonic, influenza-like illness characterized by myalgia, malaise and fever
  - Usually affects healthy individuals

Treatment

Begin treatment as soon as disease is suspected
Supportive – oxygen, fluid, and electrolyte replacement
Antibiotic therapy – usually quinolones and macrolides

Tests generally appear in the order most useful for common clinical situations

Test name: Sodium, Plasma or Serum

ARUP #: 0020001

Methodology: Quantitative Ion-Selective Electrode

Use: Non-specific testing

Test name: Phosphorus, Inorganic, Plasma or Serum

ARUP #: 0020028

Methodology: Quantitative Spectrophotometry

Use: Non-specific testing

Test name: Urinalysis, Complete

ARUP #: 0020350

Methodology: Reflective Photometry/Microscopic by Yellow IRIS

Use: Non-specific testing

Test name: CBC with Platelet Count & Automated Differential

ARUP #: 0040003

Methodology: Automated Cell Count with Flow Cell Differential

Use:

Non-specific testing

May be useful in distinguishing bacterial from viral etiologies

Test name: Hepatic Function Panel

ARUP #: 0020416

Methodology: Refer to individual components.

Use: Non-specific testing

Test name: Legionella pneumophila Antigen, Urine

ARUP #: 0070322

Methodology: Qualitative Enzyme-Linked Immunosorbent Assay

Use:

Rapid diagnostic test with good sensitivity and high specificity

Limitations:

Only detects antigens to L. pneumophila serogroup 1; however, this serogroup causes >70% of the Legionnaires’ disease cases

70% sensitivity, 100% specificity

Test name: Legionella Species by PCR

ARUP #: 0056105

Methodology: Qualitative Polymerase Chain Reaction

Use:

Rapid diagnostic test

Aid in diagnosing etiology of pneumonia when Legionella is suspected

Detects several medically relevant Legionella species, including L. pneumophila, L. micdadei, L. bozemanii, L. longbeachae, L. feeleii and L. dumoffii

Increases chances for discovery of organism in patient partially treated with empirical antibiotics

Limitations:

Only for respiratory secretions

Negative result does not rule out the presence of PCR inhibitors nor the presence of Legionella organisms in numbers lower than the limit of detection (~14 organisms/sample)

80% sensitivity, 100% specificity

Test name: Legionella Species, Culture

ARUP #: 0060113

Methodology: Standard reference procedures for Legionella culture and identification

Use:

Gold standard test

Detect different species

Limitations:

Requires 3-5 days

Most sensitive in severe disease

20-95% sensitivity, 100% specificity

Follow-up: