Lorry G. Rubin
Pneumonia caused by Legionella pneumophila or other species, known as Legionnaires disease or legionellosis, is a common cause of community-acquired pneumonia in adults and is a cause of health care-associated pneumonia and pneumonia in immunocompromised adults and children. L pneumophila may also cause Pontiac fever, an uncommon, short incubation, influenza-like illness that primarily affects adults with symptoms of fever, malaise, myalgia, chills, headache, and pleuritic pain.3-5
L pneumophila the most virulent species, causes the majority of human infections and Legionella longbeachae, Legionella bozemanii, Legionella dumoffi, and Legionella micdadei cause most of the remainder.8-10 These bacilli are nutritionally fastidious, aerobic rods that, after recovery on artificial media, stain as gram negative.
Infection with Legionella results from inhalation of contaminated aerosols from environmental or aquatic sources.11-15Legionella are not transmitted from person to person. Legionella spp are ubiquitous in natural freshwater habitats such as lakes, rivers, and groundwater. From these sources, they gain entry into water systems of buildings, including hospitals. These bacteria thrive at temperatures between 30°C (86°F) and 54°C (129.2°F) but are killed at temperatures above 60°C (140°F). Community outbreaks, almost all due to L pneumophila,8 have occurred and have been linked to aerosol-generating machinery. Health care-associated infections and outbreaks also occur and are most commonly traced to the water supply, particularly the hot water supply. Sporadic cases have often been linked to home water heaters, particularly electric water heaters.16
Most cases of Legionnaires disease occur in susceptible elderly or middle-age adults. Legionella are responsible for 1% to 15% of community-acquired pneumonias in adults that require hospitalization. The incubation period has been estimated to range from 2 to 10 days, with an average of 7 days.1
Legionellosis is uncommon in the pediatric age group. Only 40 (1.4%) of 2766 cases of legionellosis reported to the Centers for Disease Control and Prevention in 2006 were in persons 24 years of age or younger.19 In pediatric legionellosis, the risk factors for serious infection are immune compromise due to cancer therapy, corticosteroid treatment, primary immune deficiency, or underlying lung disease including health care-associated infection in children on ventilators.14,20Legionella pneumonia has been reported as a health care-associated cause of serious or fatal pneumonia in both full term and premature infants, and those with congenital heart disease.21Legionella spp are probably responsible for 1% to 3% of mild-to-moderately severe community-acquired pneumonias in healthy children.22-25 These infections may resolve without antibiotic therapy effective against these pathogens. Subclinical infection probably occurs, as evidenced by serosurvey data that anti-Legionella antibody titers increase with age.22,23
The most important clinical presentation of infection in both children and adults with legionellosis is acute lobar pneumonia presenting as an acute febrile illness with cough that may be accompanied by chest pain. Chest radiographs show evidence of alveolar, rather than interstitial, infiltrates. Disease is most often unilateral but may progress to bilateral disease. Pulmonary nodules with or without cavitation may occur, particularly in immunocompromised hosts.20,27-30 Pleural effusion may occur, but the incidence is not different from other bacterial pneumonias. Progressive respiratory distress, and often respiratory failure, develops over several days. Copathogens are rarely recovered. The fatality rate among previously healthy, appropriately treated adults is about 6%.9Legionella infection is relatively common in renal or cardiac transplant patients presenting within several weeks after transplantation with fever and pulmonary nodules on chest radiograph. Alternatively, these patients may have prodromal symptoms of malaise, myalgias, and headache, followed by an abrupt onset of dyspnea, cough, and pleuritic chest pain indicating pneumonia.31,32
In neonates, the clinical presentation is that of acute respiratory distress requiring mechanical ventilation. Because of the fulminant nature of the infection, the failure to consider this organism, and the uncommon use of empiric antimicrobial therapy active against this pathogen, the diagnosis is established in some infants only at autopsy.21,33
Extrapulmonary infection occurs rarely, with the heart a specific site of infection.26 In children, extrapulmonary infection has been found in the liver, spleen, and groin.28,34 The origin of localized extrapulmonary infection is commonly a postoperative wound that was irrigated with Legionella-contaminated water.
Nonspecific laboratory abnormalities commonly include leukocytosis with a left shift, hyponatremia, proteinuria, or elevation of liver function tests. Hyponatremia is significantly more frequent in the initial stage of legionellosis than in pneumonia caused by other etiologies. Specific laboratory diagnosis is established by culture of pulmonary secretions (the “gold standard”), by urinary antigen detection, by direct detection of organisms in pulmonary secretions, or by serology.6,35
Legionella do not grow on ordinary laboratory media and must be cultured on special medium with pretreatment of the specimen to optimize growth and inhibit overgrowth of other microorganisms.6,38Because of the difficulty of recovering the organism in culture, direct detection of bacteria or serology is frequently used to diagnose legionellosis. Detection of Legionella antigens in urine is an excellent test; with sensitivities of 80% to 90%.6,39-41 Antigen can be detected as early as a few days after onset of infection. These assays primarily detect antigen of L pneumophila serogroup 1 but are positive in urine from some patients infected with nonserogroup 1 or with other Legionellaspecies.40,41 Antigenuria is typically prolonged beyond resolution of clinical infection and should not be used to judge the adequacy of therapy.43 Detection of organisms on smears of respiratory secretions using specific antibodies by direct (or indirect) immunofluorescence (DFA) using polyclonal or monoclonal antibodies is a rapid and reasonably sensitive (average sensitivity approximately 60%) test. A polymerase chain reaction (PCR)–based assay for diagnosis is available.6 Serology by indirect immunofluorescence demonstrating a fourfold rise in antibody titer to more than 1:128 is diagnostic of legionellosis.35
Although it has been stated that infected children younger than 1 year do not seroconvert,47 seroconversion has been documented in several young children with legionellosis.23,48,49 In summary, although culture is the gold standard, detection of antigen in urine or direct detection of organisms on smears of respiratory secretions are useful tests to diagnose infection with Legionella. Detection of seroconversion is a complementary test to confirm infection.
Legionnaires disease may be fatal; therefore, appropriate therapy should be instituted promptly in suspected cases. Based on extensive but uncontrolled clinical experience, the antibiotic of choice for treatment of Legionella infection in children is intravenously administered azithromycin with intravenous erythromycin as an alternative.9,50 After a definite clinical response, oral azithromycin may be substituted to complete a 5- to 10-day course. If erythromycin is used, a 14- to 21-day course should be completed. Experience suggests that rifampin is effective in combination with azithromycin and should be considered for patients with severe infections, for those who fail to respond to azithromycin, and for severely immunocompromised patients. When treating a patient with a solid organ transplant, it is important to consider that azithromycin and erythromycin inhibit the metabolism of cyclosporine, and rifampin has the opposite effect.
Unlike erythromycin, fluoroquinolone antibiotics, such as levofloxacin, are bactericidal for Legionella and may be superior to azalide/macrolide therapy, at least in adults.9,51,52 Doxycycline and trimethoprim-sulfamethoxazole have been used successfully in some patients. β-lactam antibiotics and aminoglycosides are ineffective.
Outbreaks in hospitals are investigated by culturing hospital water sources for Legionella or detecting Legionella in water by PCR. There are three accepted methods for decontaminating the water supply: hyperchlorinating the water supply; superheating the water to between 70°C (158°F) and 80°C (176°F) with flushing of the distal sites; and installing a copper-silver ionization unit in the water supply line.53-55