Management of Community-Acquired Legionella Pneumonia

Legionella pneumonia is an infrequent, often community-acquired pneumonia (CAP) that may present occasionally to healthcare providers. The sporadic nature of this type of pneumonia may lead to the misdiagnosis as a simple pneumonia, especially in otherwise healthy individuals. Legionella pneumonia is also unique in that it is not transmitted person to person; its mode of transmission appears to be through contaminated water or inhalation of bacteria. Pneumonia has been divided into two categories: CAP and healthcare-associated pneumonia (HCAP), the latter of which includes hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Patients with these diagnoses frequently present either to the Emergency Department for hospital admission or as visitors to a primary medical practitioner seeking outpatient treatment. Additional considerations are the decisions of whether or not to admit a patient with pneumonia to an inpatient facility, and when to do so.

To accurately diagnose and treat pneumonia, practitioners need to be aware of local susceptibility and resistance patterns of common pathogens. Current hospital-based antibiograms are usually available to local practitioners for the benefit of selecting the correct antibiotic.¹

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The Infectious Diseases Society of America/American Thoracic Society guidelines define CAP, HCAP, HAP, and VAP diagnoses as follows²:

Community-acquired pneumonia:
• Patients with pneumonia who do not meet HCAP, HAP, or VAP criteria

Healthcare-associated pneumonia:
• Patients who are hospitalized for more than two days in an acute care facility within 90 days of infection, residing in a nursing home, or residing in a long-term care facility
• Patients who are attending a hospital or hemodialysis clinic
• Patients who are receiving intravenous antibiotic therapy or immunosuppressive therapy, or wound care within 30 days of infection

Hospital-acquired pneumonia:
• Patients with pneumonia occurring 48 hours or more after hospital admission

Ventilator-associated pneumonia:
• Patients with pneumonia occurring more than 48-72 hours post-intubation²
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Legionella pneumophila (Legionella) , often known as Legionnaires’ disease, is an atypical bacterial infection responsible for both CAP and HCAP in the United States. Legionella pneumophila is the most common strain for the more than 40 different strains of legionellosis, with serogroup 1 being the most likely.³ Forgie et al⁴ noted that a more accurate number is 48 species of Legionella, with approximately 24 species causing pneumonia. A German study of 2503 adult patients with CAP noted that Legionella was diagnosed in 94 patients (3.8%). Vonbaum and colleagues suggested that Legionella is the most common pathogen to cause CAP in both ambulatory and inpatient hospitalizations.⁵

Cases of Legionella may occur as part of an outbreak or in isolated instances. Pontiac fever, a milder illness caused by the Legionella bacteria, is rarely fatal, and patients are infrequently hospitalized due to its self-limiting nature. However, where there are suspected cases of Pontiac fever, there are likely cases of Legionella pneumophila present. Careful reporting of such suspicions to the local Department of Health can avoid an epidemic of either Pontiac fever or Legionella pneumophila. Legionella does not have seasonal variation; therefore, there is not an increase in outbreaks during the winter and spring. The frequency of Legionella appears to increase during the summer and early fall months. Individuals most at risk include those age 65 years or older, male, and with other comorbid illness such as neoplastic illness, chronic lung disease, liver disease, kidney disease, cerebrovascular disease, heart disease, corticosteroid use, or immunosuppression. Individuals with these risk factors frequently reside in long-term care facilities. Those who use tobacco products may also be more at risk for the disease.^6,7

This article describes the occurrence of Legionella in the community, as well as the diagnosis and management of this infectious disease.

Overview of Legionella Pneumonia

Historical Perspective
Legionella pneumophila (pneumophila meaning lung loving) is an aerobic gram-negative, cigar-shaped bacterium. The bacterium was named after an American Legion convention in Philadelphia at the Bellevue-Stratford Hotel in 1976, in which 221 individuals came down with a sudden and mysterious illness, and 34 died. Seventy-two individuals who were not a part of the convention but had either been in the hotel or walked past the hotel were also part of the 221 who became ill. The source of the illness was linked to the cooling towers of the hotel.⁸

Legionella disease had been linked to a milder infection around 1968, when patients and staff in a community health center in Pontiac, Michigan, developed violent chills, fevers, headaches, acute muscular pain, and other flu-like symptoms. The illnesses were linked to contaminated water being sprayed over the condenser coils in the air conditioning system. Through a leak in the duct system, mist from this water got into the circulating air. Scientists were puzzled about what was making these individuals ill, yet years of testing still could not determine the cause of such a disease. It was not until the Legionella outbreak in 1976 and comparison of frozen blood tests from the Pontiac illness that scientists were able to determine that the same bacteria was involved.⁹ Ninety-eight persons during the American Legion convention had a mild respiratory illness consistent with Pontiac fever. These individuals likely were not recognized or included in this outbreak of Legionnnaires’ disease.⁸

Modes of Transmission
Legionella bacteria outbreaks or isolated issues may be related to soil excavation, creeks, ponds, potable drinking water, air conditioning and air conditioning units in certain settings such as schools, whirlpool spas, cruise ships, hotels, hospitals, nursing homes, potting soil, and water used for bathing.⁶ Also included as potential sources of the bacteria are artificial fountains, water displays, offices, car washes (especially those that recirculate water), communal showers, industrial cleaning where rinsing or blowing water occurs, and paint booths.¹⁰ Supermarket misters, swamp coolers, municipal water systems, wells, and streams are also possible sources of contamination. Eighteen cases of Legionella were related to a decorative fountain outside a restaurant from June to November 2005 in Rapid City, South Dakota.¹¹ In Scotland, two individuals died after being exposed to Legionella at a cider mill of Legionella.¹² Of note, private home air conditioners or air conditioning in automobiles do not appear to be a listed source of Legionella.

Aspiration has been shown to be a mode of transmission for Legionella. Thus, individuals in long-term care facilities—especially those with permanent or temporary nasogastric tubes—need to be monitored for possible Legionella.¹³ Legionella can colonize the respiratory tract and cause pneumonia later on.¹⁴ Transesophageal echocardiography probes have also been linked to Legionella.¹⁵ Such exposures support that patients need to be questioned for possible exposure to Legionella that may not be attributed to routine health-related procedures, such as physical therapy in a whirlpool bath.

Case Reports of Legionella Pneumonia
The number of Legionella cases in the United States between 2005 and 2006 was approximately 8000-18,000 of yearly hospitalized cases of pneumonia. However, this may not be accurate data, likely because individuals with travel-related Legionellaleave the area where they contracted the infection. Thus, practitioners are not aware that there may be a Legionella case associated with the travel location or the involvement of any type of water contamination. Even a single overnight stay away from home can be significant. As a result, there may be underreporting, as well as a failure to utilize proper diagnostic testing for the Legionella.^16,17 These data did not include patients who were treated on an outpatient basis.

Making the Diagnosis

Deciding whether a patient could have been exposed to Legionella can be difficult for a provider. However, when evaluating middle-aged or elderly persons and other at-risk individuals exhibiting high fever, cough, and dyspnea, providers need to consider that they may have been exposed to Legionella, especially if they present for treatment in the summer and fall months for flu-like or pneumonia-like symptoms. In these cases, testing for Legionella is warranted through laboratory testing and a chest radiograph. Further, based upon their presentation, individuals may need to be admitted—especially if they have comorbid illness.

The presentation of Legionella pneumonia may not be immediately evident to patients and healthcare providers. Individuals may not realize the magnitude of their illness for several days, which places them at increased risk of mortality since they may not seek medical treatment until they are very ill. It is also important to determine if individuals have been treated elsewhere prior to this visit, as well as any type of “self-medication,” such as using antibiotics from a previous infection or using someone else’s medications.¹⁸ The Table provides a comparison of Legionnaires’ disease and Pontiac fever to aid practitioners in distinguishing between these two presentations.

Laboratory Tests
Identification of Legionella can be through sputum culture, paired serologic tests based on rising antibody titers, and antigen detection studies such as direct fluorescent or urinary antigen antibody.¹⁹ Laboratory confirmation includes a demonstration of a greater than fourfold increase in the antibody titer to at least 1:128 between acute and convalescent-phase serum specimens, or a demonstration of an antibody titer greater than 1024.²⁰ The diagnosis requires the use of buffered charcoal yeast media and takes days for results. Antibody screening should include both IgG and IgM because some patients will only have an IgM response.³

Legionella urinary antigen tests are readily available and results are known in a few hours.¹⁷ The urinary antigen is easier to obtain than sputum culture. One reason may be that since patients have a nonproductive cough, there is inadequate sputum to collect. Forgie et al⁴ stated that only one-third of individuals with pneumonia can produce an adequate sputum specimen. It is also more difficult to obtain sputum samples in individuals in long-term care facilities due to poor cough reflex and abnormal mental status.⁷ Legionella urinary antigen test has a sensitivity of 80% and a specificity in excess of 95%. However, a downside is that urinary antigen tests will remain positive even after appropriate antibiotic therapy, and may remain positive for up to one year. Urine tests only detect Legionella pneumophila, serogroup 1 (although this is the most common Legionnaires’ disease).³

Blázquez and colleagues²¹ concluded that overall sensitivity of urinary antigen testing in their study was 47.7% (141/295 cases). Urinary antigen sensitivity was associated with the clinical severity of pneumonia. The number of positive urinary antigen tests was highest (85.7%) among patients who had severe pneumonia and lowest (37.9%) among those with mild pneumonia. Thus, individuals with mild pneumonia may go undetected, and urinary antigen tests cannot replace other diagnostic methods.²¹

Radiological Evidence
Tan et al¹⁹ studied CAP in patients admitted to hospitals in Akron, Ohio, between November 1990 and November 1992. They discovered that 43 individuals with Legionnaires’ disease tended to have “atypical pneumonia” and presented with patchy x-rays, unilobar in either the left or right lower lobe. Most presented without an effusion. As their hospitalization progressed, they tended to have multilobar or bilateral lobar pneumonia as well as bilateral effusion on chest radiographs. Three of the 43 patients never had an abnormal chest radiograph at the time of admission or during their hospitalization.¹⁹ For patients who do not demonstrate radiographic changes, the chest radiographs may not demonstrate clearing of the pneumonia for one to four months after the diagnosis.²²

Mortality
Mortality remains high in those admitted to the Intensive Care Unit (ICU). Over 200 immunocompetent patients admitted to 33 Spanish ICUs were analyzed for CAP. Patients with nonpneumococcal CAP experienced more shock and need for mechanical ventilation. In that study, 20 patients were diagnosed with Legionella pneumophila. Seventeen of these patients were treated with adequate antibiotic therapy and three died; however, the report did not state whether the three patients who received inadequate antibiotic therapy were the persons who died.²³

Disposition

Important tools to consider when deciding whether to admit a patient for pneumonia including Legionella are the Pneumonia Severity Index (PSI)²⁴ and the British Thoracic Society Community Acquired Pneumonia Severity Score (“CURB-65”)²⁵ tests. However, a downside is that neither of these tests is used for HCAP.

Pneumonia Severity Index
The PSI is an interactive tool for the Pneumonia Severity Index from the Assessment of the Variation and Outcomes of Pneumonia: Pneumonia Patient Outcomes Research Team Final Report, and can be accessed at http://pda.ahrq.gov/clinic/psi/psicalc.asp. The tool is based on age, sex, and nursing home resident demographic factors. It includes comorbid diseases such as renal disease, liver disease, congestive heart failure, cerebrovascular disease, and neoplasia. Other physical examination criteria included are whether or not the patient has an altered mental status; systolic blood pressure less than 90 mm Hg; temperature less than 35 degrees C or greater than or equal to 40 degrees C; respiratory rate greater than or equal to 30 breaths per minute; or heart rate greater than or equal to 125 beats per minute. The criteria included in the PSI for laboratory tests are: arterial pH less than 7.35; PO₂ less than 60 mm Hg or O₂ saturation less than 90%; sodium less than 130 mmol/L; hematocrit less than 30%; glucose greater than or equal to 250 mg/dL; blood urea nitrogen (BUN) greater than or equal to 30 mg/dL; or whether a pleural effusion is present. Checking on which criteria are applicable to each patient determines the risks and possible mortality for that individual. For instance, a 45-year-old female who has a heart rate of 125 beats per minute and systolic blood pressure of less than 90 mm Hg, and sodium of less than 130 mmol/L would be low risk, class III with a score between 71 and 90 and a possible mortality of 0.9%. After quantifying the risk and mortality potential, the decision of whether to admit the patient would then be based on the provider’s clinical judgment.²⁴

British Thoracic Society Community Acquired Pneumonia Severity Score (“CURB-65”)
CURB-65 is also an interactive tool that measures illness severity based upon the presence of confusion, uremia, respiratory rate, blood pressure, and age. One point is assigned for each of the following:

Confusion (new)
Uremia (BUN ≥ 20 mg/dL [> 7 mmol/L])
Respiratory rate ≥ 30 breaths per minute
Blood pressure < 90 mm Hg systolic or ≤ 60 mm Hg diastolic
Age ≥ 65 years

Those with scores of greater than 2 should be hospitalized.²⁵ The British Thoracic Society Community Acquired Pneumonia Severity Score (“CURB-65”) can be accessed at www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Pneumonia/Guidelines/CAPQuickRefGuide-web.pdf.

Admission to the ICU
Slaven and colleagues¹ recommended that patients exhibiting three or more minor criteria including multilobar infiltrates, BUN greater than 20 mg/dL, confusion, PaO₂:FIO₂ ratio greater than or equal to 250, serum lactate greater than 4, asplenia, alcoholism/cirrhosis, and unexplained metabolic acidosis should be admitted to the ICU. Additionally, patients with a PSI class V and/or a CURB-65 score of 3 or greater will require an ICU admission.¹ Variables associated with increased mortality included shock, acute renal failure, and an Acute Physiology And Chronic Health Evaluation (APACHE) II score of 24 or greater. (APACHE II is a tool to measure the severity of disease for adult patients admitted to the ICU,^1,26 and can be accessed at www.mdcalc.com/apache-ii-score-for-icu-mortality.)

Outpatient Therapy
If a patient meets the criteria for outpatient therapy (eg, nontoxic-appearing and has no comorbid illness), consideration should be given to microbiological testing by obtaining blood cultures as well as sputum Gram staining. If Legionella pneumonia is suspected, paired serologic tests based on rising antibody titers, and antigen detection studies (eg, direct fluorescent, urinary antigen antibody) should be obtained. While there is no research evidence to support this recommendation, continued monitoring may provide clues to possible pathogens. Patients should follow up with their providers within 1-2 days for clinical reassessment. Delaying antibiotics in order to obtain sputum cultures, serologic testing, blood cultures, and urine cultures is not recommended.¹

Treatment

Parental therapy should be initiated until there is a clinical response. Levofloxacin is widely recommended since it is a potent quinolone in the intracellular model and is superior to the macrolides. In addition, moxifloxacin and gemifloxacin could be used as well as azithromycin or erythromycin.^2,27 Total duration of therapy for Legionella pneumonia is 7-10 days for azithromycin and 10-14 days for other regimens. Patients who are severely ill upon presentation or are immunocompromised should receive a total course of 21 days.²⁸ The latest standards for treatment are available for a small fee at www.antimicrobe.org.²⁹ In addition, consulting the Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults will also be helpful.² Current hospital-based antibiograms are usually available to local practitioners for the benefit of selecting the correct antibiotic.¹ Infection with the Legionella bacteria can be lethal if left untreated or if the incorrect antibiotic is ordered.

Conclusion

Legionella is among the three most common causes of severe pneumonia in the community and likely will require an ICU admission. Practitioners must be vigilant in their examination and assessment of patients. Many practitioners do not routinely ask their patients about their travel history when they present with pneumonia-like or flu-like symptoms. Further, since Legionella presents mainly in the summer and early fall months, practitioners may attribute such illness to being viral in nature.

Radiographs in Legionella are useful for the monitoring of the disease, but are not conclusive enough for diagnostic purposes. Infection with the Legionella bacteria can be lethal if left untreated or if the incorrect antibiotic is ordered. Urine antigen is a simple, quick way to make sure patients are not infected. However, this does not replace other diagnostic methods, as individuals with mild pneumonia may go undetected. Thus, it is important to include, if possible, blood cultures, sputum culture, paired serologic tests based on rising antibody titers, and antigen detection studies such as direct fluorescent in addition to urinary antigen antibody. Delaying antibiotics in order to obtain sputum cultures, serologic testing, blood cultures, and urine cultures is not recommended.

If a patient tests positive for Legionella, or if there is a high suspicion level for Legionella, then the best antibiotic therapy appears to be an active quinolone such as levofloxacin, moxifloxacin, or gemifloxacin. Alternatives include erythromycin or azithromycin. Use of the PSI, CURB-65, and APACHE II calculator^24-26 can assist in deciding which patients will need to be admitted, which patients will require ICU monitoring, and which patients should receive outpatient therapy. If patients are managed on an outpatient basis, then they need to return in 1-2 days for a clinical reassessment.

Careful detection of any possible trends in the diagnosis of Pontiac fever and Legionella is important so that epidemic outbreaks can be avoided. Reporting such trends to the local Department of Health will help our communities remain healthy as well as benefit our patients. Finally, future research regarding Legionella will include the prevalence of Legionella in long-term care facilities and tertiary centers.

Ms. Kountz is an Acute Care Nurse Practitioner, St. Elizabeth Health Center, Youngstown, OH.

The author reports no relevant financial relationships.

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