AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

An outbreak of serious pulmonary infections among people attending a convention of the American Legion in Philadelphia during the US Bicentennial celebration in July 1976 prompted the description of Legionnaires disease and its causative organism, Legionella pneumophila.

A nonpneumonic variant caused by the same species is called Pontiac fever, named for an outbreak of the described disease in Pontiac, Michigan, in 1968.

Pathophysiology

Legionella species are poorly staining, obligate, aerobic, gram-negative bacilli. Serogroup 1 is most frequently identified in clinical disease, but 18 serogroups of L pneumophila are presently known. Other than L pneumophila, 34 species of Legionella have been identified, mostly from immunocompromised patients with pneumonia.

Although pneumonia is the most common presenting problem, other pulmonary manifestations are frequent. The constitutional, cardiac, gastrointestinal, neurologic, renal, musculoskeletal, hepatic, and hematologic abnormalities variably seen with this disease are elaborated in Clinical.

Frequency

United States

Since the initial identification of 235 cases in 1976, Legionnaires disease has become recognized as the most common cause of atypical pneumonia in hospitalized patients. It is the second most common cause of community-acquired bacterial pneumonia. Legionnaires disease is reportable in the US. The Centers for Disease Control and Prevention (CDC) received reports of 1241 cases in 1995, indicating an incidence of 0.48 cases per 100,000 people. This represents passive disease surveillance. More active surveillance methods estimate that upwards of 20,000 cases occur annually in the US.

International

Outbreaks have been recognized throughout North America, Africa, Australia, Europe, and South America.

Mortality/Morbidity

• Legionnaires disease has a 25% mortality rate. However, this figure should be interpreted cautiously because of possible underreporting of comorbid disease.
• Rhabdomyolysis and renal failure may be seen in this disease.

Sex

Men are affected more frequently than women.

Age

• The weighted mean age for patients with Legionnaires disease is 52.7 years, with increasing incidence until age 79.
• The incidence in persons younger than 35 years is less than 0.1 cases per 100,000 people.
• Older patients have higher mortality rates.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Legionnaires disease is more common in the summer, especially in August, and is slightly more prevalent in the northern US.

• The classical presentation begins with an incubation period of 2-10 days.
• Patients often experience a prodrome of 1-2 days of mild headache and myalgias, followed by high fever, chills, and multiple rigors.
• Cough is present in 90% of cases; cough usually is nonproductive at first but may become productive as the disease progresses.
• Other pulmonary manifestations include dyspnea, pleuritic chest pain, and hemoptysis, which may be present in as many as one third of cases.
• Gastrointestinal symptoms include nausea, vomiting, diarrhea, and anorexia.
• Neurologic symptoms include headache, altered mental status, and rarely, focal symptoms.
• Musculoskeletal symptoms include arthralgias and myalgias.
• Nonpulmonary symptoms are prominent early in the disease.

Physical

• The vital signs may reveal high fever and tachypnea. Relative bradycardia may occur in up to 66% of patients.
• Absence of inflammation of the upper respiratory tract is common and is a clinically useful indicator.
• Chest auscultation findings may be normal or may reveal rales, rhonchi, or signs of consolidation.
• Pericarditis and endocarditis may be present.
• Hepatomegaly may be seen in rare cases.
• The neurologic examination findings or the patient's mental status may be abnormal.
• The patient may have blood-streaked sputum.
• The rest of the physical examination may be unremarkable, but signs and symptoms of risk factors for the disease should be sought.

Causes

• Investigations of outbreaks have documented aerosol transmission from contaminated water sources, including the following:
• • Cooling systems
  • Showers
  • Decorative fountains
  • Humidifiers
  • Respiratory therapy equipment
  • Whirlpool spas
• Risk factors for Legionnaires disease include the following:
• • Smoking
  • Diabetes
  • Cancer, particularly hematological or pulmonary malignancy
  • AIDS
  • End-stage renal disease
  • Chronic cardiopulmonary disease
  • Advanced age
  • Alcohol abuse
  • Surgery

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• CBC: Look for leukocytosis, left shift, hematologic malignancy, and disseminated intravascular coagulation (DIC).
• Electrolytes: Look for hyponatremia, since syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been associated with this disease.
• BUN and creatinine: Look for renal failure and dehydration.
• Liver function tests (LFTs): Look for nonspecific LFT abnormalities, which are very common in this disease and may help distinguish Legionnaires disease from other pneumonias.
• Alkaline phosphatase: Look for nonspecific depression, which along with LFT abnormalities is very common.
• Creatine phosphokinase: Look for elevation indicating rhabdomyolysis, which occasionally is seen in Legionnaires disease. The rhabdomyolysis may be so severe as to cause renal failure.
• Urinalysis: Look for proteinuria, hematuria, and renal failure.
• Sputum Gram stain: Look for increased polymorphonuclear leukocytes and monocytes without bacteria.
• Sputum and blood cultures: Although no findings will return to the ED, this will assist consultants caring for the patient.
• ABG: Look for hypoxemia.
• Serology for Legionella species: Several tests are available.
• • Urine antigen testing is highly specific and sensitive and, if available within the treatment facility, very rapid.
  • Indirect fluorescent antibody testing and nucleic acid hybridization testing also may be available.
  • Direct fluorescent antibody examination has fallen out of favor.

Imaging Studies

• Chest x-ray
• • Up to 50% of patients have a pleural effusion.
  • Chest x-ray (CXR) is not a specific test for Legionnaires disease.
  • CXR often shows patchy alveolar infiltrates with consolidation in the lower lobe.
  • May take 1-4 months for the CXR to return to normal.
  • Progression of the infiltrate may be seen despite antibiotic therapy.
• Noncontrast head CT scan
• • This is indicated for patients with altered mental status.
  • It should be normal in Legionnaires disease.

Other Tests

• Silver and Gimenez stains for lung tissue/specimens

Procedures

• Lumbar puncture: This procedure is indicated for patients with altered mental status. In uncomplicated Legionnaires disease, the cerebrospinal fluid (CSF) findings are generally normal.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Oxygen therapy is the mainstay of prehospital therapy.
• Intravenous (IV) access and fluid therapy may be indicated for dehydration.
• Restraints may be required for patients with altered mental status. Seizure precautions may be indicated.
• Differentiating Legionnaires disease with multiple rigors and altered mental status from a seizure disorder may be possible only through a clinical examination.

Emergency Department Care

• Control the airway as indicated clinically. Support ventilation and oxygenation.
• Rehydrate the patient as indicated, especially in diarrheal disease.
• Antipyretics may be used, as indicated.
• Cardiac monitoring may be required if chest pain, hypotension, bradycardia, or other indicators are present.
• Obtain laboratory specimens, CXR, CT scan, and CSF, as indicated.
• Begin empiric antibiotic therapy as noted below.

Consultations

• Because of the protean presentation of this disease, many different consultations may be indicated.
• General internists, pulmonologists, critical care specialists, cardiologists, gastroenterologists, neurologists, infectious disease specialists, nephrologists, oncologists, and general surgeons may be required at one time or another.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Standard antibiotic susceptibility tests are not reliable in Legionnaires disease. Erythromycin, with or without rifampin, is the DOC for Legionnaires disease, but the combined GI manifestations of the disease added to the GI effects of erythromycin may be problematic. For this reason, some specialists prefer to start with doxycycline. Other drugs include cotrimoxazole, tetracycline, and ciprofloxacin. The new fluoroquinolone and macrolide drugs may be indicated, but their efficacy has not been established.

Drug Category: Antibiotics

Therapy must cover all likely pathogens in the context of the clinical setting.

Drug Name	Doxycycline (Doryx, Bio-Tab)
Description	Second DOC; interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity against susceptible bacteria.
Adult Dose	200 mg IV/PO loading dose, followed by 100 mg IV/PO bid; do not inject IM/SC
Pediatric Dose	<8 years: Not recommended <100 lb (45 kg): 2 mg/lb/d (4.4 mg/kg/d) IV/PO divided bid >100 lb (45 kg): Administer as in adults
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can increase hypoprothrombinemic effects of anticoagulants; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Rifampin (Rifadin, Rimactane)
Description	DOC to use with erythromycin. Inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, interacts with bacterial RNA polymerase, but does not inhibit mammalian enzyme.
Adult Dose	600 mg PO/IV qd
Pediatric Dose	10-20 mg/kg PO/IV; not to exceed 600 mg/d
Contraindications	Documented hypersensitivity
Interactions	Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; BP may increase with enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Obtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Hospital admission is indicated in almost all patients.
• ICU admission should be based on clinical judgment of current severity of illness, presence of comorbid disease, general health of the patient, and availability of adequate patient monitoring.
• Consultation with a pulmonologist or infectious disease specialist is strongly recommended.

Further Outpatient Care

• Close follow-up with a pulmonologist or infectious disease specialist is recommended following discharge.

Transfer

• Transfer may be indicated for patients presenting to facilities without adequate ICU facilities, pulmonary consultants, or infectious disease specialists.

Deterrence/Prevention

• Heating water to 60-70 degrees centigrade may help prevent water contamination.
• Ultraviolet light or copper silver ionization is bactericidal.

Complications

• Dehydration
• Hyponatremia due to SIADH
• Respiratory insufficiency
• Endocarditis
• DIC
• Renal failure
• Multiple organ failure
• Coma
• Death in 10% of treated nonimmunocompromised patients and in as many as 80% of untreated immunocompromised patients
• Bacteremia or abscess formation in immunocompromised patients

Prognosis

• Recovery is variable.
• Some patients experience rapid improvement, while others have a much more protracted course despite treatment.
• The mortality rate approaches 50% with nosocomial infections.
• Data concerning the overall prognosis of patients are unreliable because of the high rate of serious comorbid diseases.

Patient Education

• Altering modifiable risk factors is beneficial.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize the disease in the absence of upper respiratory symptoms
• Failure to hospitalize patients suspected of having Legionnaires disease, especially those with comorbid diseases
• Failure to consider the diagnosis in patients with altered mental status, fever, and normal CSF studies
• Failure to initiate antibiotic therapy
• Failure to monitor for rhabdomyolysis

Special Concerns

• Pregnancy: Avoid tetracyclines.
• Pediatric: Fortunately, Legionnaires disease is unusual in this group.
• Geriatric: Aggressive therapy may be indicated due to the higher mortality rate.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Amsden GW. Treatment of Legionnaires' disease. Drugs. 2005;65(5):605-14. [Medline].
• Blanquer J, Blanquer R, Borras R, et al. Aetiology of community acquired pneumonia in Valencia, Spain: a multicentre prospective study. Thorax. Jul 1991;46(7):508-11. [Medline].
• CDC. Legionnaires disease associated with a whirlpool spa display--Virginia, September-October, 1996. MMWR Morb Mortal Wkly Rep. Jan 31 1997;46(4):83-6. [Medline].
• CDC. Summary of notifiable diseases, United States 1995. MMWR Morb Mortal Wkly Rep. Oct 25 1996;44(53):1-87. [Medline].
• Cunna B. Legionnaire's disease - Case studies in infectious disease. Emerg Med. 1992;24:227-234. [Medline].
• Falco V, Fernandez de Sevilla T, Alegre J, et al. Legionella pneumophila. A cause of severe community-acquired pneumonia. Chest. Oct 1991;100(4):1007-11. [Medline].
• Lane G, Ferrari A, Dreher HM. Legionnaire''s disease: a current update. Medsurg Nurs. Dec 2004;13(6):409-14. [Medline].
• Marrie TJ, Haldane EV, Noble MA, et al. Causes of atypical pneumonia: results of a 1-year prospective study. Can Med Assoc J. Nov 15 1981;125(10):1118-23. [Medline].
• Marston BJ, Lipman HB, Breiman RF. Surveillance for Legionnaires'' disease. Risk factors for morbidity and mortality. Arch Intern Med. Nov 14 1994;154(21):2417-22. [Medline].
• Palmer L. Legionella pneumonia - Cardiopulmonary problems in the office. Emerg Med. 1992;24:84-94. [Medline].
• Reingold AL. Role of legionellae in acute infections of the lower respiratory tract. Rev Infect Dis. Sep-Oct 1988;10(5):1018-28. [Medline].
• Shah A, Check F, Baskin S, et al. Legionnaires'' disease and acute renal failure: case report and review. Clin Infect Dis. Jan 1992;14(1):204-7. [Medline].

Article Last Updated: Oct 10, 2006