Legionnaires Disease

Background

Legionnaires disease (LD) is the pneumonia caused by Legionella pneumophila. Legionnaires disease also refers to a more benign, self-limited, acute febrile illness known as Pontiac fever, which has been linked serologically to L pneumophila, although it presents without pneumonia. Pontiac fever usually is self-limiting and typically does not require antibiotics administration.^{[1, 2, 3, 4]}  

L pneumophila is an important cause of nosocomial and community-acquired pneumonia (CAP) and must be considered a possible causative pathogen in any patient who presents with atypical pneumonia. Empiric antibiotic coverage for CAP usually includes classes of antibiotics that have Legionella coverage such as fluroquinolones, macrolides and tetracyclines.

The Legionella bacterium first was identified in the summer of 1976 during the 58th annual convention of the American Legion, which was held at the Bellevue-Stratford Hotel in Philadelphia. Infection was presumed to be spread by contamination of the water in the hotel's air conditioning system. The presentation ranged from mild flulike symptoms to multisystem organ failure. Of the 182 people infected, 29 died.

Although Legionella was not identified until 1976, L pneumophila subsequently was found in a clinical specimen dating to 1943 and, according to retrospective analysis, may have been responsible for pre-1976 pneumonia epidemics in Philadelphia; Washington, DC; and Minnesota.

Legionnaires disease is the term that collectively describes infections caused by members of the Legionellaceae family.

Bacterial characteristics

The Legionella bacterium is a small, aerobic, waterborne, gram-negative, unencapsulated bacillus that is nonmotile, catalase-positive, and weakly oxidase-positive. It is a fastidious organism and does not grow anaerobically or on standard media. Buffered charcoal yeast extract (CYE) agar is the primary medium used for isolation of the bacterium.^{[1, 2, 3, 4]}  

The Legionellaceae family consists of more than 42 species, constituting 64 serogroups. L pneumophila is the most common species, causing up to 90% of the cases of Legionellosis, followed by L micdadei (otherwise known as the Pittsburgh pneumonia agent), L bozemanii, L dumoffii, and L longbeachae. Fifteen serogroups of L pneumophila have been identified, with serogroups 1, 4, and 6 being the primary causes of human disease. Serogroup 1 is thought to be responsible for 80% of the reported cases of legionellosis caused by L pneumophila.^[5]

Patient education

For patient education information, see Bronchoscopy.

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Pathophysiology

Legionella species are obligate or facultative intracellular parasites. Water is the major environmental reservoir for Legionella; the bacteria can infect and replicate within protozoa such as Acanthamoeba and Hartmannella, which are free-living amoebae found in natural and manufactured water systems. (Legionellae can resist low levels of chlorine used in water distribution systems.)^[4]

Within the amebic cells, Legionella species can avoid the endosomal-lysosomal pathway and can replicate within the phagosome. Surviving and growing in amebic cells allows Legionella to persist in nature. 

View Image

This electron micrograph depicts an amoeba, Hartmannella vermiformis (orange), as it entraps a Legionella pneumophila bacterium (green) with an extend....

Legionella species infect human macrophages and monocytes; intracellular replication of the bacterium is observed within these cells in the alveoli. The intracellular infections of protozoa and macrophages have many similarities.^[4]

Activated T cells produce lymphokines that stimulate increased antimicrobial activity of macrophages. This cell-mediated activation is key to halting the intracellular growth oflegionellae. The significant role of cellular immunity explains why legionellae are observed more frequently in immunocompromised patients. Humoral immunity is thought to play a secondary role in the host response to Legionella infection.

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Etiology

Legionella transmission is thought to occur via inhalation of aerosolized mist from water sources, such as the following, that have been contaminated with the bacterium^{[4, 6, 7, 8, 9]} :

• Cooling systems
• Showers
• Decorative fountains
• Humidifiers
• Respiratory therapy equipment
• Whirlpool spas
• Ice machines
• Potting soil (L longbeachae spp) 
• Compost (L longbeachae spp) 
• Roadside puddles
• Tubs used for water births^[10]

Legionnaires disease (LD) may be travel associated from exposure in aircraft or hotel facilities. Person-to-person transmission, however, has not been documented.

The highest incidence of LD occurs during late spring and early fall, when air-conditioning systems are used more frequently.^{[11, 12]} Nosocomial acquisition likely occurs via aspiration, respiratory therapy equipment,^[8] or contaminated water. In addition, transmission has been linked to the use of humidifiers, nebulizers, and items that were rinsed with contaminated tap water.

The following features increase the likelihood of colonization and amplification of legionellae in human-made water environments:

• Temperature of 25-42°C
• Stagnation
• Scale and sediment
• Presence of certain free-living aquatic amoebae capable of supporting intracellular growth of legionellae

Risk factors

The risk for infection increases with the type and intensity of the exposure, as well as the health status of the exposed individual. Numerous factors increase the risk of acquiring Legionella infections, including the following:

• Advanced age
• Smoking
• Chronic heart or lung disease
• Immunocompromised hosts with impaired cell-mediated immunity (eg, acquired immunodeficiency syndrome [AIDS]) or immunosuppressive medication use (especially corticosteroids)
• Diabetes
• Hematologic malignancies
• End-stage renal disease
• Alcohol abuse

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Epidemiology

Occurrence in the United States

Legionnaires disease (LD) has a reported incidence of 8000-18,000 cases per year. In certain geographic areas, community-acquired LD is more common. Although LD is reportable in all 50 states, it is estimated that only 5-10% of cases are reported. Although most cases of the disease are sporadic, 10-20% are linked to outbreaks. Legionnaires disease is more common in the summer, especially in August, and is slightly more prevalent in the northern United Sates.^{[1, 2, 4]}

Prevalence reports for Legionella have increased with time, likely due to the availability of more effective testing modalities. However, it also is possible that Legionella infections are increasing in frequency for environmental, population-based, or behavioral reasons.

Legionnaires disease is among the top 3-4 microbial causes of CAP, constituting approximately 1-9% of patients with CAP who require hospitalization. Legionnaires disease is an even more common cause of severe pneumonia in patients who require admission to an intensive care unit (ICU), ranking second, after pneumococcal pneumonia, in such cases. In addition, it is recognized as the most common cause of atypical pneumonia in hospitalized patients.

Legionnaires disease cases acquired in the hospital usually occur as outbreaks and most often result from the presence of Legionella in water sources and on surfaces (eg, pipes, rubber, plastics). The organism also is found in water sediment, which may explain its ability to persist despite flushing of hospital water systems.^{[13, 14]}

Barsky et al compared epidemiological patterns of LD cases reported to the US Centers for Disease Control and Prevention before and during a rise in cases. The average age-standardized incidence was 0.48 cases per 100,000 population from 1992 to 2002, significantly increasing to 2.71 cases per 100,000 in 2018. Reported cases increased across all demographic groups, and the rise was more substantial in groups with initially higher incidence rates. White individuals accounted for the largest number of cases overall, but Black or African-American individuals had the highest incidence rate. Incidence and increases were most notable in the East North Central, Middle Atlantic, and New England regions. Seasonality, particularly in the Northeast and Midwest, became more pronounced from 2003 to 2018. The rising incidence of Legionnaires' disease was prominently linked to increasing racial disparities, geographical concentration, and seasonality.^[15]

International occurrence

Legionnaires disease is thought to occur worldwide and to be the cause of 2-15% of all CAP cases that require hospitalization. Outbreaks have been recognized throughout North America, Africa, Australia, Europe, and South America.

Sex- and age-related demographics

Men have a greater risk of acquiring L pneumophila infection. Older age is another risk factor; the weighted mean age for patients with LD is 52.7 years, with increasing incidence until age 79 years. Mortality rates also are higher in older patients. The incidence of LD in persons younger than 35 years is less than 0.1 cases per 100,000 people.

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Prognosis

Recovery is variable in Legionnaires disease (LD); some patients experience rapid improvement, whereas others have a much more protracted course despite treatment. The mortality rate approaches 50% with nosocomial infections.^[4]

Progressive respiratory failure is the most common cause of death in patients with Legionella pneumonia. However, the mortality rate depends on the comorbid conditions of the patient, as well as on the choice and timeliness of antibiotics administration. The site of acquisition (eg, nosocomial, community-acquired) also may affect the outcome.

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Complications

Potential complications include the following^[4] :

• Decreased pulmonary function
• Fulminant respiratory failure
• Dehydration, septic shock
• Hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
• Respiratory insufficiency, hypoxic respiratory failure
• Endocarditis
• Neurologic symptoms: Including lethargy, headache, altered mental status, and nonfocal neurologic examination findings
• Gastrointestinal symptoms: Diarrhea, vomiting
• Renal failure
• Rhabdomyolysis
• Multiple organ failure
• Coma
• Bacteremia or abscess formation (in the lungs or at extrapulmonary sites) in immunocompromised patients
• Death: In 10% of treated nonimmunocompromised patients and in as many as 80% of untreated immunocompromised patients

A study by van Loenhout et al that included 190 patients with LD found that a year after the disease’s onset, many patients were still suffering from 1 or more adverse health effects, particularly fatigue and reduced general quality of life.^[16]

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History

Legionella pneumophila causes 2 distinct disease entities. Legionnaires disease (LD) is characterized by pneumonia. Pontiac fever is a short-term, milder illness than LD and is not characterized by pneumonia, instead manifesting as fever and myalgias that resolve without treatment. Extrapulmonary legionellosis such as pericarditis, endocarditis and cellulitis, although not common, has been reported in both immunocompromised and immunocompetent patients and can occur as isolated cases or in the setting of Legionella pneumonia. Species other than L pneumophila usually have been implicated in these cases.^{[17, 18]}

The incubation period in LD ranges from 2-10 days. Patients who develop Legionella infection and who have been hospitalized continuously for 10 or more days before the onset of illness are classified as having definite nosocomial LD. Patients with laboratory-confirmed infection that develops 2-9 days after hospitalization are classified as having possible nosocomial LD. Nosocomial LD occurs in clusters.

For patients with pneumonia, the following indications warrant testing for Legionnaires' disease:

• Outpatient antibiotic failure for community-acquired pneumonia
• Severe pneumonia, in particular illness requiring intensive care
• Presence of an immunocompromising condition
• Overnight travel away from the home during incubation period
• Risk factors and hospitalization with healthcare-associated pneumonia
• Overnight stay in a healthcare facility during incubation period
• Epidemiologic link to a setting with known Legionella concerns

Settings of concern include those where Legionella has been identified or association with at least one laboratory-confirmed Legionnaires' disease case.

Symptoms of LD can occur as follows:

• Patients often experience a prodrome of 1-2 days of mild headache and myalgias, followed by high fever, and chills
• 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 (watery, not bloody), abdominal pain, and anorexia
• Neurologic symptoms include headache, lethargy, encephalopathy, altered mental status (the most common neurologic symptom), and rarely, focal symptoms
• Musculoskeletal symptoms include myalgias
• Nonpulmonary symptoms are prominent early in the disease

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Physical Examination

Manifestations of Legionnaires disease (LD) may include the following:

• Headache
• Mental status changes
• Fever greater than 40°C, or 102°F (range, 38.8-40.5°C)
• Relative bradycardia (excluding patients with pacemakers or arrhythmias or those receiving beta blockers, diltiazem, or verapamil)
• Myocarditis
• Prosthetic valve endocarditis
• Tachypnea
• Localized rales
• Blood-streaked sputum
• Extrapulmonary manifestations
• Abdominal pain
• Pancreatitis
• Acute renal failure

A clinical point score may be helpful in increasing the probability of correctly diagnosing LD and prompting specific/definitive LD testing.

Table 1. Legionnaires Disease: Six Clinical Predictors and Diagnostic Eliminators in Adults Admitted with Pneumonia ^a

View Table

See Table

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Complications

Legionnaires disease

Hospitalization for Legionnaires' disease (LD) is common. The case-fatality rate is approximately 10%; however it averages 25% for healthcare-associated infections.^[19]  

Pontiac fever

Hospitalization is uncommon for patients with Pontiac fever, and the case-fatality rate is very low.^[19]

Severe Legionnaires disease

Although LD accounts for only about 5% of community-acquired pneumonia cases, it is a leading cause of pneumonia requiring ICU admission.^[20] Mortality rates can be as high as 40% in certain patient groups despite appropriate treatment. Recent studies have shown high levels of Legionella DNA in severe cases, along with immune response and lung microbiome impairments. Diagnosis has improved with urinary antigen testing and molecular methods. Treatment involves macrolides, quinolones, or a combination, particularly in severe cases. Factors influencing mortality include ICU admission, immune status, and infection source. Research on biomarkers and therapies is needed to address the rising incidence and severity of LD.

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Approach Considerations

For patients with pneumonia, the following indications justify testing for Legionnaires' disease:

• Failure of outpatient antibiotic treatment for community-acquired pneumonia
• Severe pneumonia, especially illness requiring intensive care
• Having an immunocompromising condition
• Traveling away from home overnight during the incubation period 
• Risk factors and hospitalization with healthcare-associated pneumonia
• Staying in a healthcare facility overnight during the incubation period 
• Epidemiologic link to a setting where Legionella is a concern^[2]

Settings of concern include those where Legionella has been identified or association with at least one laboratory-confirmed Legionnaires' disease case.

It is crucial to conduct testing for healthcare-associated Legionnaires disease (LD) if any of the following conditions are found within a healthcare facility:

• Diagnosis of healthcare-associated LD disease in other patients within the past year   
• Positive environmental tests indicating the presence of Legionella bacteria in the past 2 months     
• Recent alterations in water quality that could promote the growth of Legionella, such as low chlorine levels^{[2, 21]}

Although pneumonias caused by numerous pathogens share similar laboratory findings, hyponatremia (sodium < 130 mEq/L) secondary to the syndrome of inappropriate antidiuretic hormone (SIADH) is more common in LD than in pneumonias secondary to other pathogens; however, this is not specific for LD.

Other nonspecific laboratory findings in LD include the following^[2] :

• Early/mildly elevated liver enzymes
• Highly elevated erythrocyte sedimentation rate (ESE) (>90 mm/h)
• Highly elevated ferritin levels (>2 times normal)
• Increased C-reactive protein (CRP) levels (>30 mg/L
• Hypophosphatemia (specific to LD excluding other causes of hypophosphatemia)^[22]
• Microscopic hematuria

Severe disease is defined by respiratory failure, bilateral pneumonia, rapidly worsening pulmonary infiltrates, or the presence of at least 2 of the following 3 characteristics^[20] :

• Blood urea nitrogen (BUN) greater than or equal to 30 mg/dL     
• Diastolic blood pressure lowere than 60 mm Hg
• Respiratory rate greater than 30/min

Most recognized Legionnaires' disease outbreaks are associated with:

• Healthcare settings: Hospitals, long-term care facilities^[2]
• Travel: Hotels, resorts, cruise ships^[2]

Racial disparities

Hunter et al conducted a narrative review of articles that focused on disparities in the incidence of LD and pneumonia (inclusive of bacterial pneumonia and/or community-acquired pneumonia) among adults and children (excluding articles that were limited to people aged < 18 years).^[23]  

NNDSS data from 2014-2018 highlight racial disparities in LD incidence, with Black individuals having nearly double the rate compared to White individuals in 2018. In New York City, non-Hispanic Black residents in high-poverty areas had the highest rates of the disease, reflecting similar disparities in other types of pneumonia. Whereas risk factors for LD are well-known, understanding the reasons behind racial and socioeconomic disparities and implementing interventions to address them remain understudied. Social determinants of health, such as economic stability, education access, social context, healthcare quality, and neighborhood environments, play a significant role in determining health outcomes and quality of life. Healthy People 2030 categorizes these determinants into five domains to guide efforts in addressing health inequities.^[23]  

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Histologic Findings

Typically, Legionella histopathologic lesions are found in interstitial lining and alveoli with polymorphonuclear cells and macrophages.

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Laboratory Studies

General tests in Legionnaires disease (LD) can include the following:

• Complete blood count (CBC): Look for leukocytosis, left shift
• Look for elevated ESR
• Electrolytes: Look for hypophosphatemia and hyponatremia
• BUN and creatinine: Look for renal failure and dehydration
• Liver function tests (LFTs): Look for nonspecific LFT abnormalities, which are very common in LD and may help to distinguish it from other atypical pneumonias
• Look for highly elevated serum ferritin
• Creatine phosphokinase: Look for elevation indicating rhabdomyolysis, which occasionally is seen in LD; the rhabdomyolysis may be so severe as to cause renal failure
• Arterial blood gas (ABG): Look for hypoxemia
• Gram stain: Typically, many leukocytes and a paucity of organisms are observed; if visible, the organisms are small, faintly staining, gram-negative bacilli
• Sputum Gram stain: Look for increased polymorphonuclear leukocytes and monocytes without bacteria
• Urinalysis: Look for proteinuria, hematuria, and renal failure

Culture of respiratory secretions

The gold standard for diagnosing Legionella infection is isolating the organism in respiratory secretions using specialized media like buffered charcoal yeast extract agar. Legionella, a slow-growing organism, forms colonies with a distinct ground-glass appearance within 3-5 days.^{[3, 21]}

Sputum cultures have an 80% sensitivity and 100% specificity, with increased sensitivity achieved through transtracheal aspiration or bronchoscopy. Bronchoalveolar lavage (BAL) fluid yields higher diagnostic success compared to bronchial wash specimens.

The recommended diagnostic tests for Legionnaires' disease are lower respiratory secretion culture and the Legionella urinary antigen test, with serological tests generally discouraged. Simultaneous performance of both sputum culture and urinary antigen tests is advised. While pre-antibiotic sputum sampling is ideal, treatment initiation should not be delayed. The urinary antigen test can detect Legionella post-treatment, primarily targeting Legionella pneumophila serogroup 1.

Culture is essential for identifying other Legionella species and facilitating public health investigations. Molecular techniques can link clinical and environmental isolates to pinpoint outbreak sources.

Blood cultures

Legionella can be isolated from blood, but it shows a much lower sensitivity.

Amplification with polymerase chain reaction (PCR) assay

Polymerase chain reaction assay of urine, serum, and BAL fluid is very specific for the detection of Legionella, but the sensitivity is not greater than that of culture. The primary benefit of this procedure, like immunofluorescent antibody (IFA) titers, is that it can be used to detect infections caused by legionellae other than L pneumophila serogroup 1.

Direct fluorescent antibody staining of sputum

Direct fluorescent antibody staining is a rapid test that yields results in 2-4 hours, but it has a lower sensitivity and has fallen out of favor. The specificity of DFA is 96-99% using monoclonal antibody instead of polyclonal antibody.

A positive result depends on finding large numbers of organisms in the specimen; therefore, the sensitivity is increased when samples from the lower respiratory tract are used. Results of DFA testing rapidly become negative (in 4-6 d).^{[3, 21]}

Serology

The most widely used tests include the IFA and enzyme-linked immunosorbent assay (ELISA) tests. A single increased antibody titer confirms LD if the IFA titer is greater than or equal to 1:256.

Although LD serologic tests are the most readily available, they require a 4-fold increase in antibody titer (to 1:128 or greater), which takes 4-8 weeks. Paired measurements from both the acute and convalescent periods should be obtained, since an antibody response may not be apparent for up to 3 months. Of note, antibody levels do not increase in approximately one third of patients with LD.^{[3, 21]}

Urinary antigen testing

The Legionella lipopolysaccharide antigen is detected with ELISA, radioimmunoassay (RIA), and the latex agglutination test. The Legionella lipopolysaccharide antigen becomes detectable in 80% of patients on days 1-3 of clinical illness. The urinary antigen assay can be used to detect only L pneumophila (serogroup 1).^[24]

The advantages of urinary antigen testing include rapidity and simplicity. In addition, the relative ease of obtaining a urine sample compared with obtaining sputum specimens and the persistence of antigen secretion in patients who are on antibiotic therapy increase the usefulness of the urine antigen detection method.^[24]

The urinary antigen test initially may be negative, but when positive it can remain positive for months after the acute episode has resolved.^[24]

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Imaging Studies

Radiography

Legionella infection almost always produces an abnormal chest radiographic finding, with the abnormalities typically being unilateral and occurring in the lower lobes. However, the abnormalities are variable and may be focal or diffuse; no typical radiographic presentation exists for LD.^[25]

Rapidly progressive, asymmetrical infiltrates nonetheless are characteristic of the disease. Chest radiography often shows patchy alveolar infiltrates with consolidation in the lower lobe (although all lobes may be affected). Progression of the infiltrates may be seen despite antibiotic therapy. Up to 50% of patients have a pleural effusion. Cavity and abscess formation are rare in LD but can occur in immunocompromised hosts.

Improvement revealed on chest radiography can lag behind clinical improvement by 5-7 days; the radiographic abnormalities can take up to 3-4 months to resolve completely.

Noncontrast head CT scanning

Noncontrast head computed tomography (CT) scanning is indicated for patients with altered mental status. Findings should be normal in LD.

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Procedures

Bronchoscopy

Bronchoscopy with or without bronchoalveolar lavage (BAL) may be helpful in establishing or excluding the diagnosis if respiratory culture specimens are difficult to obtain. Bronchoalveolar lavage fluid gives a higher yield than bronchial wash specimens.

Lumbar puncture

Lumbar puncture is indicated for patients with altered mental status. In uncomplicated LD, the cerebrospinal fluid (CSF) findings generally are normal.

Thoracentesis

If a pleural effusion is present, fluid can be evaluated using DFA or LD culture.

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Approach Considerations

A delay in treatment significantly increases the risk for mortality in Legionnaires disease (LD). Therefore, include empiric anti-Legionella therapy in the regimen for severe community-acquired pneumonia and in specific cases of nosocomial pneumonia.

Although Legionella pneumonia can present as a mild illness, most patients require hospitalization with parenteral antibiotics. Most healthy hosts exhibit clinical response to treatment within 3-5 days.

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Prehospital and Emergency Department Care

Prehospital care

Oxygen therapy is the mainstay of prehospital therapy in Legionnaires disease (LD). Intravenous (IV) access and fluid therapy may be indicated for dehydration or septic shock. Restraints may be required for patients with altered mental status. Seizure precautions may be indicated.

Differentiating LD with multiple rigors and altered mental status from a seizure disorder may be possible only through a clinical examination.

Emergency department care

Patient management includes the following:

• Control the airway as indicated clinically; support ventilation and oxygenation
• Rehydrate the patient as indicated, especially in shock or 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 (respiratory culture and urine antigen testing), chest radiographs, computed tomography (CT) scans, and cerebrospinal fluid (CSF), as indicated
• Begin empiric antibiotic therapy

Also see the Legionella home page from the Centers for Disease Control and Prevention (CDC), as well as the Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults.^[1]

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Inpatient Care

Patients with mild to moderate pneumonia are admitted to the hospital for parenteral antibiotics and supportive measures. Patients deemed to have a severe pneumonia may require admission to the intensive care unit (ICU) for closer monitoring. Quickly initiate empiric antibiotic treatment and obtain a diagnostic workup.

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

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Antibiotic Therapy

In milder cases, patients can be treated in an outpatient setting with oral antibiotics that are targeted against Legionella and are bactericidal, have long half-lives, and achieve high lung tissue concentrations. First line agents would include levofloxacin (a fluroquinolone) and azithromycin (a macrolide) administered through the oral route. Alternative agents would include other fluroquinolones such as ciprofloxacin, moxifloxacin, and doxycycline (a tetracycline). Other macrolides would include clarithromycin, erythromycin, and roxithromycin. Tetracyclines such as tigecycline have been used as second line agents against L pneumoniae but appear to have limited activity against L longbeachae and therefore, should be avoided if this strain is suspected.^[26]

For patients with L longbeachae infection, a fluroquinolone or a macrolide should be used. Treatment duration can range from 5-10 days in mild cases.

For patients with moderate or severe infection that requires hospitalization, or those who cannot tolerate oral medications, the intravenous (IV) route of administration is preferred. When patients become clinically stable and can tolerate orally, they can be transitioned to the oral equivalent. For severe disease, a fluoroquinolone is recommended. Adding rifampin to a regimen of fluroquinolone or macrolide has not been shown to have any additional benefits.^[27] . 

Continue oral antibiotics on an outpatient basis for 14-21 days, depending on the severity of the presenting illness. Patients should receive close follow-up care to ensure complete resolution of their respiratory symptoms.

Patients should complete the full course of antibiotics, whether the treatment is initiated in the outpatient setting or in the hospital. 

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Consultations

Consultation with a pulmonologist or infectious disease specialist is strongly recommended in cases of Legionnaires disease (LD). Because of the protean presentation of this disease, however, consultations with other specialists, including the following, may be required at one time or another:

• General internist
• Critical care specialist
• Cardiologist
• Gastroenterologist
• Neurologist
• Nephrologist
• Oncologist
• General surgeon

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Deterrence and Prevention

Prevention and control of nosocomial legionellosis

Legionella should be sought in hospitalized patients with an increased risk for infection and subsequent death. If 1 definite case or 2 possible cases of nosocomial Legionnaires disease (LD) occur among inpatients, initiate an investigation for a hospital source.

Legionella transmission also can be discouraged through the routine maintenance of cooling towers and the use of only sterile water for filling and rinsing nebulization devices. Improved design and maintenance of cooling towers and plumbing systems can help.

Disinfection

Superheating water to 70-80°C, with flushing of distal sites, may help to prevent water contamination.

Copper-silver ionization units—which produce metallic ions that disrupt the bacterial cell wall, thus resulting in lysis and cell death—are very effective at eradicating Legionella; they provide sustained protection.

Ultraviolet light kills legionellae by damaging cellular deoxyribonucleic acid (DNA). This modality is effective when disinfecting localized areas, but because it provides no sustained protection, adjunctive treatments must be used.

Hyperchlorination of water is not recommended, because Legionella is fairly chlorine resistant, and chlorine decomposes at the higher temperatures found in the hot water systems it is used to treat.

Following reports of Legionnaires disease (LD) in newborns who were infected during water births,^[10] the Arizona Department of Health Services issued recommendations for minimizing the risk for Legionella contamination in tubs used during the water birthing process, such as flushing out stagnant water and sediment from hoses by running hot water through them for 3 minutes before using them to fill the tub.^[28]

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Clinical Guidance for Legionella infections by the US Centers for Disease Control and Prevention

Clinical Guidance for Legionella infections by the CDC are summarized below^[2] :

Legionnaires disease cannot be clinically or radiographically distinguished from pneumonia caused by other pathogens.                                     

Appropriate testing is essential for accurate diagnosis and treatment decisions.                                                                                                       

The first-line treatment for healthcare-associated or community-acquired pneumonia may not always include Legionella-directed antibiotics.

Indications for Legionnaires disease testing include the following: 

• Outpatient antibiotic failure for community-acquired pneumonia
• Severe pneumonia requiring intensive care
• Presence of an immunocompromising condition
• Overnight travel during the incubation period
• Risk factors and hospitalization for healthcare-associated pneumonia

Defining the incubation period:

• Public health officials collect exposure histories for the 14 days before symptom onset for surveillance purposes.

Testing for healthcare-associated Legionnaires' disease is crucial if identified factors in a healthcare facility include the following:

• Healthcare-associated Legionnaires' disease diagnosis in the last year
• Positive environmental tests for Legionella
• Recent changes in water quality conducive to Legionella growth

The majority of Legionnaires' disease outbreaks are associated with the following:

• Healthcare settings like hospitals and long-term care facilities
• Travel-related settings such as hotels, resorts, and cruise ships

Diagnostic tests for Legionnaires disease include the following:

• Culture of lower respiratory secretions
• Legionella urinary antigen test

Specimen collection best practice is to obtain sputum for culture and urine for the urinary antigen test concurrently.

• Treatment options differ for Legionnaires' disease and Pontiac fever, with antibiotic treatment typically not recommended for Pontiac fever as it is self-limited and resolves within a week.

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Medication Summary

Mild Legionnaires disease can be treated with a single oral antibiotic regimen that has activity against Legionella pneumophila including fluroquinolones such as levofloxacin, and moxifloxacin, macrolides like azithromycin, clarithromycin. Other tetracyclines like doxycycline can also be used as an alternative therapy.

In suspected cases of Legionella longbeachae infection, either a fluroquinolone or a macrolide antibiotic should be used. Tetracyclines are not very effective against this strain of Legionella and should be avoided.

In patients with severe disease that require hospitalization, intravenous (IV) antibiotics should be used initially and then consider changing to oral antibiotic therapy with a 10- to 14-day course after patients begin to show signs of clinical improvement. A 14-21-day course is recommended in patients who are immunocompromised, who have severe underlying disease, or who develop complicated Legionella pneumonia. 

For immunosuppressed patients, fluoroquinolone therapy is recommended as first line. If unable to use a fluoroquinolone, azithroycin can be used. For those on immunosuppressive medications, dose reduction may be required. The fatality rate of Legionella pneumonia is high in this patient population.

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Levofloxacin (Levaquin)

• Dosing, Interactions, etc.

Clinical Context:  Levofloxacin, a fluoroquinolone, is used for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.

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Azithromycin (Zithromax, Zmax)

• Dosing, Interactions, etc.

Clinical Context:  Azithromycin is a macrolide antibiotic used to treat mild to moderate microbial infections.

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Ciprofloxacin (Cipro, Cipro XR)

• Dosing, Interactions, etc.

Clinical Context:  Ciprofloxacin is a fluoroquinolone with activity against pseudomonads, streptococci, methicillin-resistant Staphylococcus aureus (MRSA), S epidermidis, and most gram-negative organisms, but with no activity against anaerobes. It inhibits bacterial DNA synthesis and, consequently, bacterial growth.

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Doxycycline (Vibramycin, Adoxa, Avidoxy, Doryx, Monodox)

• Dosing, Interactions, etc.

Clinical Context:  Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

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Moxifloxacin (Avelox)

• Dosing, Interactions, etc.

Clinical Context:  Moxifloxacin inhibits bacterial DNA synthesis and growth. Its activity is similar to that of ciprofloxacin and levofloxacin.

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Rifampin (Rifadin)

• Dosing, Interactions, etc.

Clinical Context:  Rifampin can be used with erythromycin although it is not routinely recommended. It inhibits DNA-dependent RNA polymerase activity in susceptible cells by interacting with bacterial RNA polymerase (without inhibiting the mammalian enzyme).

• References

Tigecycline (Tygacil)

• Dosing, Interactions, etc.

Clinical Context:  A glycylcycline that inhibits protein synthesis by binding to the 30S ribosomal subunit of susceptible bacteria. It has demonstrated activity against both gram-positive and gram-negative anaerobes, as well as against gram-positive aerobic strains such as methicillin-resistant staphylococci, streptococci, and enterococci.

• References

Erythromycin base (Ery-Tab, E.E.S., PCE)

• Dosing, Interactions, etc.

Clinical Context:  Erythromycin inhibits ribonucleic acid (RNA) ̶ dependent protein synthesis, possibly by stimulating dissociation of peptidyl transfer RNA (tRNA) from ribosomes. This inhibits bacterial growth.

• References

Clarithromycin (Biaxin, Biaxin XL)

• Dosing, Interactions, etc.

Clinical Context:  Clarithromycin is a macrolide antibiotic that inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

• References

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

• References