Legionnaires’ Disease– Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

The term Legionnaires’ disease was coined for an epidemic of lower respiratory tract disease occurring among people attending an American Legion convention in Philadelphia in 1976. The previously unknown causative bacterium was identified and named Legionella pneumophila; it may cause pneumonia or flulike illness:

  • Ranks among the 3 most common pneumonias in the clinical setting
  • System(s) affected: GI; Pulmonary
  • Synonym(s): Legionella pneumonia; Legionellosis

Epidemiology

  • Predominant age: 15 months–84 years old; increased >50 years old
  • Predominant sex: Male > Female

Incidence

  • True incidence is not well known
  • Probably only 2–10% of cases are reported.
  • May increase with the rise in population density in some urban areas, hotel, or cruise ship stays within previous 2 weeks and more complex infrastructures
  • Outbreaks occur most often at the end of the summer and early fall.

Risk Factors

  • Smoking
  • Alcohol abuse
  • Immunosuppression/HIV
  • Chronic cardiopulmonary disease
  • Surgery
  • Advanced age
  • Renal failure
  • Fever >39°C
  • Hyponatremia
  • Liver dysfunction
  • Creatine kinase elevation

General Prevention

  • Heating water to 60–70°C may help prevent water contamination.
  • Ultraviolet light or copper-silver ionization are bactericidal.
  • Monochloramine disinfection of municipal water supplies is associated with decreased risk for Legionella infection (1)[B].

Etiology

  • Legionella pneumophila, a weak gram-negative organism, is a saprophytic water bacterium, which is widely distributed in soil and water. Serogroups 1, 2, and 6 account for most of the cases. The optimum temperature for growth is 40–45°C. It can also be associated with organic material in sediment.
  • Mode of transmission:
    • Aerosolization
    • Aspiration
    • Direct instillation into the lungs by equipment (such as respiratory equipment)
    • Most important mode: Aerosolization and airborne dissemination of contaminated water
    • Patients may acquire by inhaling organisms while showering
  • Recently, community outbreaks have been associated with whirlpools, spas, and fountains.

Commonly Associated Conditions

Pontiac fever: Self-limited flulike illness without pneumonia caused by Legionella species

municipal water supplies, legionella pneumonia, respiratory tract disease, cardiopulmonary disease, respiratory equipment, renal failure, hyponatremia,

Diagnosis

  • Range of illness from asymptomatic seroconversion, mild febrile illness, to severe pneumonia
  • Incubation 2–10 days
  • Fever, chills
  • Malaise, weakness, lethargy
  • Anorexia
  • Myalgia
  • Headache
  • Watery diarrhea in up to 50%
  • Nausea and vomiting in 10–20%
  • Dry cough, which may become productive
  • Pleuritic chest pain in up to 33%
  • Relative bradycardia in up to 67% of patients
  • Neuropsychiatric symptoms of confusion, disorientation, obtundation, depression, hallucinations, insomnia, seizures in up to 25%
  • Blood-streaked sputum; gross hemoptysis rare
  • Hyponatremia
  • Hypophosphatemia
  • Elevated serum transaminases
  • Elevated creatine kinase
  • ∼50% of hospitalized patients present with PO2 <60 mm Hg.
  • Hypotension (17%)
  • Wound infections with Legionella have been reported.

History

  • Elicit immunosuppression risk factors.
  • Elicit characteristics about cough (may not be productive).
  • Chest pain with hemoptysis can occur.
  • GI symptoms with diarrhea and nausea are frequent.

Physical Exam

Rales with signs of consolidation. Fever is usually present.

Diagnostic Tests & Interpretation

Lab

Initial lab tests

  • Gold standard is sputum culture for Legionella. Alert lab about possible diagnosis (buffered charcoal yeast extract agar) (2,3)[C].
  • Urinary antigen detects serogroup 1 (which causes most human disease) (2)[B].
  • Urinary antigen tests are highly specific (99%) but variably sensitive (74%) (4)[A].
  • The combination of respiratory specimen cultures and urine Legionella antigen testing is optimal for diagnosis.
  • Silver and Gimenez stains for lung tissue/specimens
  • Disorders that may alter lab results: Direct immunofluorescence can cross-react with Pseudomonas and Bacteroides sp., E. coli, and Haemophilus.
  • Nonspecific abnormalities may include renal and hepatic dysfunction, thrombocytopenia, hyponatremia, and hematuria.

Imaging

Initial approach

Chest radiograph (3)[B]:

  • Not specific for Legionella
  • Commonly with lower lobe patchy alveolar infiltrate with consolidation, usually unilateral
  • Cavitation or abscess, especially in immunocompromised
  • Pleural effusion in up to 50%
  • May take from 1–4 months for the radiograph to return to normal. Progression of infiltrate may be seen despite antibiotic therapy.

Diagnostic Procedures/Surgery

Transtracheal aspiration or bronchoscopy for sputum/lung samples may be needed.

Pathological Findings

  • Multifocal pneumonia with alveolitis and bronchiolitis, with fibrinous pleuritis; may have serous or serosanguineous pleural effusion
  • Abscess formation occurs in up to 20% of patients.
  • Progression of infiltrates, despite appropriate therapy, may be suggestive of Legionnaires’ disease. Also, improvement on radiograph may not correlate with clinical findings (longer lag times on radiographic findings).

Differential Diagnosis

  • Other bacterial pneumonias
  • Atypical pneumonias with mycoplasma and chlamydia
  • Viral pneumonias

Treatment

Medication

First Line

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  • Antibiotics that achieve high intracellular concentrations are most effective (macrolides, rifampin, tetracyclines, and quinolones) (2,3)[C]
  • Levofloxacin is the preferred agent (5)[B].
  • Levofloxacin 750 mg IV per day (switch to p.o. when patient is afebrile) times 10–14 days
  • Azithromycin 500 mg IV per day p.o. times 7–10 days
  • Addition of rifampin: 600 mg q12h p.o. or IV; this should be provided along with the above recommendations in very ill patients.
  • Contraindications: Hypersensitivity reactions
  • Precautions: Liver disease
  • Significant possible interactions:
    • Can increase theophylline, carbamazepine, and digoxin levels; can increase activity of oral anticoagulants
    • May decrease the effectiveness of oral anticoagulants, steroids, digoxin, quinidine, oral contraceptives, and hypoglycemic agents
  • Longer courses of treatment of up to 21 days may be needed in immunocompromised patients.

Second Line

  • Erythromycin 30–60 mg/kg/d p.o. or IV, divided into 4 doses for 10–21 days
  • May be used along with rifampin:
    • 100 mg q12h IV for 2 doses, then 100 mg b.i.d., or p.o. 200 mg for 1 dose, then 100 mg b.i.d.
    • 100 mg IV or p.o. q12h
  • Sulfamethoxazole IV or p.o.: 5 mg/kg TMP q8h

Additional Treatment

General Measures

  • The severity of the illness and the support available in the outpatient setting will dictate the appropriate site for care.
  • Supportive care
  • Maintaining oxygenation, hydration, and electrolyte balance while providing antibiotic therapy
  • There is a higher chance of extrapulmonary complications and higher mortality in AIDS patients.

In-Patient Considerations

Admission Criteria

  • Inability to tolerate oral antibiotics
  • Hypoxemia

Discharge Criteria

  • Afebrile
  • Able to tolerate oral antibiotics

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

  • Respiratory status, hydration, and electrolyte status should be monitored closely.
  • A chest radiograph is not useful to monitor the clinical response.

Patient Education

  • Educate patients regarding prevention/avoidance measures, lowering their risk status, and, if infected already, about the expected course of the disease.
  • Disease prevention: Elimination of the pathogens from water supplies
  • Person-to-person transmission has not been observed.

Prognosis

  • Recovery is variable; some patients experience rapid improvement with defervescence in 3–5 days and recovery is complete in 6–10 days, whereas others may have a much more protracted course despite treatment.
  • Mortality rate can approach 50% with nosocomial infections.

Complications

  • Dehydration
  • Hyponatremia
  • Respiratory insufficiency requiring ventilator support
  • Endocarditis (most common extrapulmonary site)
  • Disseminated intravascular coagulation
  • Renal failure
  • Multiple organ dysfunction syndrome (MODS)
  • Coma
  • Death occurs in 10% of treated nonimmunocompromised patients and in up to 80% of untreated immunocompromised patients.
  • Bacteremia or abscess formation occurs in immunocompromised patients.
  • Extrapulmonary disease can occur in the form of:
    • Encephalitis
    • Cellulitis
    • Sinusitis
    • Pancreatitis
    • Pyelonephritis
    • Endocarditis
    • Pericarditis
    • Perirectal abscess

References

1. Flannery B, Gelling LB, Vugia DJ, et al. Reducing Legionella colonization in water systems with monochloramine. Emerg Infect Dis. 2006;12:588–96.

2. Yzerman EP, den Boer JW, Lettinga KD, et al. Sensitivity of three urinary antigen tests associated with clinical severity in a large outbreak of Legionnaires’ disease in The Netherlands. J Clin Microbiol.2002;40:3232–6.

3. Tan MJ, Tan JS, Hamor RH, et al. The radiologic manifestations of Legionnaire’s disease. The Ohio Community-Based Pneumonia Incidence Study Group. Chest. 2000;117:398–403.

4. Shimada T, Noguchi Y, Jackson JL, Miyashita J, Hayashino Y, Kamiya T, Yamazaki S, Matsumura T, Fukuhara S. Systematic Review and Metaanalysis: Urinary Antigen Tests for Legionellosis. Chest. 2009 Mar 24.

5. Blázquez Garrido RM, Espinosa Parra FJ, Alemany Francés L, Ramos Guevara RM, Sánchez-Nieto JM, Segovia Hernández M, Serrano Martínez JA, Huerta FH et al. Antimicrobial chemotherapy for Legionnaires disease: levofloxacin versus macrolides. Clin Infect Dis. 2005;40:800–6.

Additional Reading

Committee on Infectious Diseases of American Academy of Pediatrics. Red Book. Elk Grove Village: American Academy of Pediatrics; 2006:417–18.

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 Inf Dis. 2007;44:S27–72.

See Also (Topic, Algorithm, Electronic Media Element)

Pneumonia, Bacterial

Codes

ICD9

482.84 Pneumonia due to legionnaires’ disease

Snomed

  • 312403005 Legionnaires’ disease (disorder)
  • 195889001 Legionella pneumonia (disorder)

Clinical Pearls

  • Consider Legionnaires’ disease in pneumonia in presence of GI symptoms, especially diarrhea; neurologic findings, especially confusion; fever >39°C; gram stain of respiratory secretions with many neutrophils but few organisms; hyponatremia.
  • Consider Legionnaires’ disease in nosocomial pneumonia.

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