Legionnaires' Disease (Legionella Infection)


Article Author:
Mark Brady


Article Editor:
Vidya Sundareshan


Editors In Chief:
Yvonne Carter
Jason Wallen


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Pritesh Sheth
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes
Kavin Sugumar


Updated:
10/27/2018 12:31:41 PM

Introduction

The 1976 American Legion Convention marked the discovery of Legionnaires' disease, a syndrome of pneumonia caused by Legionella. Many people became sick at this convention which sparked an investigation to uncover the cause. Legionella is an aerobic gram-negative bacillus that is spread through aerosolized water particles. It is a common cause of community-acquired and hospital-acquired pneumonia.[1][2][3]

  • Legionnaires' disease is caused by Legionella pneumophila. Pontiac fever refers to a benign, self-limited, acute febrile illness which is linked serologically to L pneumophila. 
  • L pneumophila causes community-acquired and nosocomial pneumonia and should be considered as a pathogen in any patient with atypical pneumonia. 
  • The Legionella bacterium was first identified in 1976 during the 58th annual convention of the American Legion in Philadelphia. Infection was thought to spread the disease by contamination of the water in the air conditioning system. Patients developed symptoms ranging from flu-like symptoms to multisystem organ failure. Of the 182 infected, 29 died.
  • Legionnaires' disease describes infections caused by the Legionellaceae family.
  • The Legionella bacterium is a small, aerobic, waterborne, gram-negative, unencapsulated bacillus that is nonmotile and oxidase and catalase positive.
  • Legionella bacterium is a fastidious organism and will not grow anaerobically on a standard media. Buffered charcoal yeast extract agar is the medium used for isolation of the bacterium.
  • The Legionellaceae consists of more than 42 species. L. pneumophila is the most common species, and it causes 90% of the cases of legionellosis, followed by L. micdadei, L. bozemanii, L. dumoffii, and L. longbeachae
  • Fifteen serogroups of L. pneumophila have been identified, with serogroups 1, 4, and 6 identified as the causes of human disease. Serogroup 1 is thought to be responsible for 80% of the reported cases.

Etiology

The family Legionellaceae has more than 50 species and more than 70 serogroups; the L. pneumophila serogroup is the most common. This bacterium grows best on buffered charcoal yeast extract agar, which is a specialized media. It inhibits the growth of other bacteria.[4]

Epidemiology

L. pneumophila is found in large bodies of water including streams and lakes. However, its growth is increased in the presence of human-made reservoirs. Risk factors include cigarette smoking and chronic lung disease.[5]

Pathophysiology

The bacterium binds to respiratory epithelial cells and alveolar macrophages after which it enters the cell. Once it has gained entry into the cell, it inhibits phagosome-lysosome fusion, thereby promoting its proliferation. 

Histopathology

Legionellae histopathologic lesions are typically found in the alveoli with polymorphonuclear cells and macrophages and in the intestinal lining.

History and Physical

The length of time between exposure and symptom onset is two to 10 days but may be up to 20. Among those exposed, between 0.1% to 5% develop the disease, while among those patients in the hospital, 0.4% to 14% develop the disease.

Patients present with fever, chills, and a dry or wet cough producing sputum. One-third of those affected cough up blood. Some also have muscle aches, headache, tiredness, loss of appetite, loss of coordination (ataxia), chest pain, or diarrhea and vomiting, and neurological symptoms including confusion and impaired cognition. Relative bradycardia also may be present, which is low or low-normal heart rate despite the presence of a fever.

Evaluation

Early diagnosis of Legionnaires' disease has shown to decrease mortality. Therefore, early diagnosis and treatment are important for survival. In patients where Legionella is suspected, urine antigen testing and sputum culture are recommended. Urine antigen testing has proven to be a quick diagnostic test with a sensitivity of more than 85% and specificity of more than 99%. However, it only tests for Legionella pneumophila serogroup, the most common serogroup to cause infection. Sputum culture takes three to five days to grow; however, this can identify other serotypes or species if present.[6][7][8]

Testing

Chest X-ray - May show pneumonia with consolidation at the base of the lungs. 

Laboratory Findings

Expect the following:

  • Hypophosphatemia
  • Hyponatremia (sodium less than 130 mEq/L) secondary to the syndrome of inappropriate antidiuretic hormone is more common in Legionnaires disease than in most cases of pneumonia that are secondary to other pathogens
  • Microscopic hematuria
  • Elevated liver enzymes
  • Elevated erythrocyte sedimentation rate (greater than 90 mm/h)
  • Elevated ferritin levels (greater than 2X normal)
  • Elevated C-reactive protein levels (greater than 30 mg/L)

Severe Disease

Expect respiratory failure, bilateral pneumonia, pulmonary infiltrates, and the presence of at least two of the following:

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

Treatment / Management

Given that this is an intracellular organism, antibiotics should be chosen that would be able to enter the cell effectively. The recommended classes of antibiotics include fluoroquinolones, macrolides, and rifampin. Either Levofloxacin 750 mg, one tablet for seven to ten days, or Azithromycin, 1 gm on day one followed by 500 mg one tablet once a day for seven to 10 days, are advised. Parenteral therapy is advised initially as the patient may not tolerate antibiotics given by mouth because of potential gastrointestinal symptoms. Immunocompromised patients, especially transplant patients, should preferably be treated for 21 days with fluoroquinolones. Macrolides would not be recommended here as they can interfere with immunosuppressant agents.[9][10][11]

To prevent the infection, most hospitals across the country perform frequent testing of their water supply for Legionella. Proper decontamination of the water supply is recommended.

Disinfection

  • Heat water to 70 C to 80 C, with flushing of distal sites.
  • Copper-silver ionization units are effective at eradicating legionellae, and they provide sustained protection.
  • Ultraviolet light kills legionellae.
  • Hyperchlorination of water is not effective because legionellae are fairly chlorine resistant, and chlorine decomposes at the higher temperatures.

Prevention

  • Legionellae transmission can be minimized through the use of only sterile water for filling and rinsing nebulization devices and regular maintenance of cooling towers.

Differential Diagnosis

Patients with Legionella pneumonia are not typically co-infected with other organisms. The differential diagnoses include atypical pathogens, Chlamydophila pneumoniae, tularemia, and Coxiella burnetii. L. pneumophila bacterium is a definite pathogen; its isolation indicates infection.

The differential diagnosis of Legionnaires disease includes:

  • Acute respiratory distress syndrome
  • Aspiration pneumonia
  • Bacterial pneumonia
  • Bronchitis
  • Empyema
  • Gastroenteritis
  • Heart failure
  • HIV disease
  • Immunocompromised pneumonia
  • Influenza
  • Meningitis
  • Pleural effusion
  • Prostatitis
  • Respiratory distress 
  • Septic shock
  • Typical, atypical, and severe community-acquired pneumonias
  • Viral pneumonia
  • Q Fever

Prognosis

The prognosis of patients with Legionnaire's disease depends on patient comorbidity, when the condition was diagnosed and how soon the treatment was instituted. In seniors, the mortality rates can vary from 10-50%.[12]

Respiratory failure is a common cause of death.

Complications

  • Acute respiratory failure
  • Shock
  • Dehydration
  • Endocarditis
  • Neurological deficits
  • GI symptoms like diarrhea
  • Renal failure
  • Coma
  • Rhabdomyolysis
  • Multiple organ failure
  • Sepsis
  • Death

Postoperative and Rehabilitation Care

Legionnaire's disease is usually managed as an inpatient. Some patients may require total parenteral antibiotics, assistance from mechanical ventilation and even enteral nutrition. close monitoring is required as sudden respiratory distress is common.

Consultations

  • Critical care specialist
  • Neurologist
  • Gastroenterologist
  • Cardiologist
  • General surgeon
  • Infectious disease consultant

Deterrence and Patient Education

Once a diagnosis of Legionella pneumonia is made, one must identify the source to prevent other patients from acquiring the organism. The air-conditioning system and nebulizing devices must be checked to identify the source of the bacteria.

Disinfection of the water by heating and use of UV light is known to kill the organism.

Pearls and Other Issues

Multiple outbreaks can be traced back to water supplies. The most recent was in 2015, and it involved multiple U.S. states. The outbreak was controlled with timely and proper testing and decontamination of the local water sources.

Enhancing Healthcare Team Outcomes

Legionella pneumonia is a serious respiratory tract infection which usually affects the elderly. If the diagnosis is missed or treatment is delayed the morbidity and mortality are very high. Learned evidence-based experience from previous outbreaks reveals that an interprofessional group of healthcare workers is vital to help decrease the morbidity of the infection. Even if a single case is diagnosed, urgent set up of a multidisciplinary team is necessary to determine the source of the outbreak. The organism is known to rapidly disseminate via air droplets and can quickly infect many people. 

The team should include a pulmonologist, infectious disease specialist, critical care specialist and an internist. The nurses play a vital role in the monitoring of the patient in the ICU.[13][14] (Level V) The pharmacist has to be up to date on the current antibiotics used to treat the infection and be aware of alternatives in case of resistance or patient intolerance.

Outcomes

The outcomes for patients with Legionella pneumonia do vary, but despite treatment, mortality rates of 5-15% are reported.[11][15] (Level V) There should be no delay in treatment as the infection is rapidly progressive and can result in multiorgan failure. Evidence-based medicine reveals that only through an integrated, streamlined approach can the mortality be reduced.


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Legionnaires' Disease (Legionella Infection) - Questions

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What is the major difference between Legionnaire disease and Pontiac fever?



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Which of the following is the preferred treatment for children with suspected or confirmed Legionella pneumonia?



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An elderly patient from a nursing home is found to have pneumonia. It appears that the air conditioning system in the home was contaminated and it is believed that the pneumonia was caused by an aerosolized organism. Given the suspected pathogen, empiric therapy with which of the following antibiotics is most appropriate?



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False positive results for Coxiella burnetii may occur in patients who develop which of the following?



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Legionnaires' disease is often associated with which of the following?



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In a 55-year-old with pneumonia and renal and hepatic abnormalities, which organism would most likely be cultured in his blood?



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Legionella pneumophila can rarely cause community acquired pneumonia in healthy children, and infection usually resolves without treatment with effective antibiotics. Legionella pneumophila is likely to cause severe and fatal disease in children with which of the following conditions?



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What kind of bacteria is Legionella pneumophila?



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A 58-year-old patient suddenly develops dyspnea, fever, general malaise, headache, and confusion. Which of the following infections presents in such a fashion?



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What is the drug of choice for Legionella pneumonia?



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Which of the following characteristics is true of Legionella infections?



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What is the vector of transmission for Legionella pneumophila?



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Which of the following organisms can be a cause of relative bradycardia with pneumonia?



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A heating, ventilating, and air conditioning technician presents with fever, nonproductive cough, and shortness of breath. The patient's occupation places him at increased risk for respiratory infection with which of the following organisms?



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Which of the following is not a characteristic of Legionella?



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Which of the following is related to the cause of Legionnaires disease?



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What is the most likely pathogen for a patient with pneumonia, renal, and hepatic abnormalities?



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Which of the following would be the appropriate first-line treatment for an adult infected with Legionella?



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Which of the following would be indicated first line for a patient with Legionnaires disease?



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Legionnaires' Disease (Legionella Infection) - References

References

Stypułkowska-Misiurewicz H,Czerwiński M, Legionellosis in Poland in 2016 Przeglad epidemiologiczny. 2018     [PubMed]
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Herwaldt LA,Marra AR, Legionella: a reemerging pathogen. Current opinion in infectious diseases. 2018 Aug     [PubMed]
Hlavsa MC,Cikesh BL,Roberts VA,Kahler AM,Vigar M,Hilborn ED,Wade TJ,Roellig DM,Murphy JL,Xiao L,Yates KM,Kunz JM,Arduino MJ,Reddy SC,Fullerton KE,Cooley LA,Beach MJ,Hill VR,Yoder JS, Outbreaks Associated with Treated Recreational Water - United States, 2000-2014. MMWR. Morbidity and mortality weekly report. 2018 May 18     [PubMed]
Hamilton KA,Prussin AJ 2nd,Ahmed W,Haas CN, Outbreaks of Legionnaires' Disease and Pontiac Fever 2006-2017. Current environmental health reports. 2018 May 9     [PubMed]
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Peter A,Routledge E, Present-day monitoring underestimates the risk of exposure to pathogenic bacteria from cold water storage tanks. PloS one. 2018     [PubMed]
Zahran S,McElmurry SP,Kilgore PE,Mushinski D,Press J,Love NG,Sadler RC,Swanson MS, Assessment of the Legionnaires' disease outbreak in Flint, Michigan. Proceedings of the National Academy of Sciences of the United States of America. 2018 Feb 20     [PubMed]
Kampitak T, Fever of unknown origin due to Legionnaires' disease: A diagnostic challenge. Travel medicine and infectious disease. 2018 Mar - Apr     [PubMed]
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Sivagnanam S,Podczervinski S,Butler-Wu SM,Hawkins V,Stednick Z,Helbert LA,Glover WA,Whimbey E,Duchin J,Cheng GS,Pergam SA, Legionnaires' disease in transplant recipients: A 15-year retrospective study in a tertiary referral center. Transplant infectious disease : an official journal of the Transplantation Society. 2017 Oct     [PubMed]
Miyashita N,Higa F,Aoki Y,Kikuchi T,Seki M,Tateda K,Maki N,Uchino K,Ogasawara K,Kiyota H,Watanabe A, Clinical presentation of Legionella pneumonia: Evaluation of clinical scoring systems and therapeutic efficacy. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2017 Nov     [PubMed]
Dunn CE,Bhopal RS,Cockings S,Walker D,Rowlingson B,Diggle P, Advancing insights into methods for studying environment-health relationships: a multidisciplinary approach to understanding Legionnaires' disease. Health     [PubMed]
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