Microbiology & infectious diseases
Gram negative bacteria
Legionella
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PubMed Search: Legionella
Table of Contents
Definition / general | Essential features | Epidemiology | Sites | Pathophysiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Immunofluorescence images | Positive stains | Electron microscopy images | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Chen T, Garrett EM. Legionella. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/microbiologylegionella.html. Accessed December 25th, 2024.
Definition / general
- Fastidious Gram negative rods associated with freshwater reservoirs that can cause respiratory infections such as Legionnaires disease and Pontiac fever
Essential features
- Fastidious, environmental Gram negative rods associated with freshwater reservoirs such as cooling towers and plumbing
- Legionella pneumophila is the primary cause of legionellosis such as Legionnaires disease and the milder Pontiac fever; while mostly environmental, several other species can cause infection, usually pulmonary
- Recovery in culture requires specialized media; urinary antigen is useful for identifying L. pneumophila serotype 1 infection, which is most common
Epidemiology
- Legionella species are widely present in natural (ponds, stream, lakes) and manmade (plumbing, cooling towers, hot tubs, showers, sprinklers) freshwater sources (Annu Rev Pathol 2020;15:439)
- Can survive in heated water with temperatures up to 55 °C as well as in treated and chlorinated water
- Can grow and multiply within freshwater amoeba, which may protect bacterium from environmental stresses
- Factors associated with bacterial growth include warm water, stagnant water and lack of disinfectant (CDC: Legionnaires' Disease & Pontiac Fever [Accessed 16 July 2024])
- Infection may be sporadic or as outbreaks resulting from exposures of many people to aerosolized, contaminated water (CDC: Legionella (Legionnaires' Disease and Pontiac Fever) [Accessed 7 May 2024])
- First identified from an outbreak of pneumonia following an American Legion convention in 1976
- No person to person transmission
- Estimates of the incidence of legionellosis range from 2 to 12% of all community acquired pneumonia (CAP) (Infect Dis Clin North Am 2017;31:111, Medicine (Baltimore) 2013;92:51)
- Attack rate of exposed populations as high as 30%
- Risk factors include age (≥ 55 years)
- L. pneumophila is the cause of 85% of legionellosis (J Infect Dis 2002;186:127)
- Serotype 1 most common
- Other species causing infection include L. micdadei, L. longbeachae, L. bozemanii; incidence varies globally (Microorganisms 2021;9:291)
Sites
- Nearly all cases of legionellosis are pulmonary (Annu Rev Pathol 2020;15:439)
- Extrapulmonary infection is rare (J Clin Med 2022;11:6126)
Pathophysiology
- Infection begins with inhalation of aerosolized water or mist containing Legionella
- Infects alveolar macrophages following phagocytosis then replicates within Legionella containing vacuoles (Annu Rev Pathol 2020;15:439, J Clin Med 2022;11:6126)
- Utilizes a type IV secretion system (T4SS) to avoid degradation and subvert host cell functions
- T4SS and type II secretion systems (T2SS) deliver bacterial toxins and effector proteins that modulate apoptosis, mimic ubiquitination and attenuate immune response
- Legionella's biphasic lifecycle includes intracellular replicative phase followed by transmissive phase (extracellular) after exhaustion of host cell nutrients (Virulence 2021;12:1122)
- Infection induces inflammatory response including activation of toll-like receptors (TLR), inflammasomes and production of proinflammatory cytokines (Virulence 2021;12:1122)
Diagrams / tables
Images hosted on other servers:
Life cycle of Legionella pneumophila
Clinical features
- 2 overlapping clinical presentations (J Clin Med 2022;11:6126)
- Pontiac fever: nonpneumonic, flu-like illness with fever, malaise and myalgia; generally self limiting, lasting 2 - 5 days
- Legionnaires disease: mild to severe pneumonia (Infect Dis Clin North Am 2017;31:111, J Clin Med 2022;11:6126)
- Often not distinguishable from other bacterial pneumonias
- May have gastrointestinal symptoms, hemoptysis (~30%), hyponatremia, elevated transaminases and C reactive protein (CRP)
- 5 - 10% mortality rate in treated patients
Diagnosis
- PCR of respiratory specimens is highly sensitive and specific (Infect Dis Ther 2022;11:973, Carroll: Manual of Clinical Microbiology, 12th Edition, 2019)
- Few commercially available assays (BioMérieux: The BioFire® FilmArray® Pneumonia (PN) Panel [Accessed 7 May 2024])
- Urinary antigen immunoassays are rapid and highly specific for L. pneumophila serotype 1
- Does not detect other Legionella species or serotypes
- Culture of sputum, bronchoalveolar lavage (BAL), pleural fluid
- Direct exam of respiratory specimens
- Gram stain of sputum frequently shows no organisms but many polymorphonuclear neutrophils (PMNs)
- Gram stain criteria for suitability of sputum for routine bacteria culture should not by applied to those submitted for Legionella culture
- Direct fluorescence antibody (DFA) lacks sensitivity and specificity in low prevalence populations
- Gram stain of sputum frequently shows no organisms but many polymorphonuclear neutrophils (PMNs)
- IgM / IgG / IgA serology; seroconversion may take 4 - 8 weeks and does not occur in all cases
Laboratory
- Buffered charcoal yeast extract (BCYE) agar is the preferred media for culture (Carroll: Manual of Clinical Microbiology, 12th Edition, 2019)
- May include antibiotics to reduce growth of normal respiratory flora
- Poor growth on blood agar, no growth on MacConkey
- Incubation 35 °C up to 14 days; colonies usually appear between 2 and 5 days
- Identification
- Gram stain: Gram negative, faintly staining
- May be short rods to long filaments; pleomorphic
- Stain poorly with safranin counterstain
- L. micdadei is the only Legionella species that is modified acid fast stain positive
- Colony morphology: smooth white-gray, may have ground glass or iridescent appearance
- May be identified by MALDI-TOF
- Gram stain: Gram negative, faintly staining
Case reports
- 9 year old girl with extrapulmonary L. micdadei (Pediatr Infect Dis J 2002;21:1174)
- 46 year old man requiring extracorporeal membrane oxygenation (ECMO) with L. pneumophila diagnosed by metagenomic next generation sequencing (mNGS) (Front Med (Lausanne) 2021;8:686512)
- 79 year old immunocompetent men with L. longbeachae pneumonia (Neth J Med 2018;76:294)
- Nosocomial outbreak of L. pneumophila from contaminated plumbing (Clin Infect Dis 2016;62:273)
Treatment
- Antibiotic susceptibility testing not routinely performed due to lack of standardized methods and poor correlation with clinical outcomes (Carroll: Manual of Clinical Microbiology, 12th Edition, 2019)
- Recommended antibiotics are macrolides (azithromycin, clarithromycin) or fluoroquinolones (ciprofloxacin, levofloxacin), alone or in combination (Infect Dis Ther 2022;11:973)
Clinical images
Contributed by Elizabeth M. Garrett, Ph.D.
Legionella pneumophila on agar
Gross description
- Legionella infection mainly involves lung tissue but with disseminated infection it can affect multiple organs
- Usually, organs involved show necrotizing exudative disease, such as focal or massive consolidation of lung, necrotic foci and abscess formation (BMC Infect Dis 2021;21:532)
Gross images
Images hosted on other servers:
Lung pathology
Microscopic (histologic) description
- Legionella infection may be identified histologically in biopsy or autopsy tissues
- Characteristic histologic features are leukocytoclastic inflammatory infiltrate of macrophages or combined macrophages and neutrophils
- In Legionella pneumonia, diffuse alveoli damage is common; septic vasculitis and focal septal disruption can be seen
- Tissue Giemsa stain or silver stains (such as Warthin-Starry or Steiner stains) may show bacteria (Ann Clin Lab Sci 1979;9:353, Kradin: Diagnostic Pathology of Infectious Disease, 2nd Edition, 2017)
Microscopic (histologic) images
Contributed by Elizabeth M. Garrett, Ph.D.
Legionella pneumophila Gram stain
Images hosted on other servers:
Silver stain, lung tissue
Immunofluorescence images
Images hosted on other servers:
Paraffin sections of lungs
Positive stains
- Silver stains such as Warthin-Starry, Steiner, Dieterle silver stain
- L. micdadei is unique among Legionella species for being modified acid fast stain positive
Electron microscopy images
Images hosted on other servers:
Legionella pneumophila
Differential diagnosis
- Other organisms causing pulmonary infection, pneumonia:
- Generally recoverable in routine bacterial culture:
- Klebsiella pneumoniae:
- Gram negative rod, short
- Streptococcus pneumoniae:
- Gram positive cocci in pairs and chains
- Haemophilus influenzae:
- Gram negative coccobacillus
- Klebsiella pneumoniae:
- Diagnosed using molecular or antigen testing:
- Influenza A and other respiratory viruses
- Chlamydophila (formerly Chlamydia) pneumoniae
- Mycoplasma pneumoniae
- Associated with aquatic sources:
- Nontuberculous mycobacteria:
- Pseudomonas aeruginosa:
- Gram negative rod
- Generally recoverable in routine bacterial culture:
Board review style question #1
A 63 year old man presents with a 2 day history of fever, dyspnea, cough and diarrhea. Radiographs show patchy, unilobar infiltrates consistent with pneumonia. Cultures are ordered. After 3 days, a Gram negative, faintly staining organism that is growing well on buffered charcoal yeast extract (BCYE) agar but not blood agar is identified (as shown in the image above). What is the most likely identification?
- Klebsiella pneumoniae
- Legionella pneumophila
- Nocardia nova
- Streptococcus pneumoniae
Board review style answer #1
B. Legionella pneumophila is a fastidious, Gram negative organism that prefers growth on BCYE and grows poorly on other media. Answer A is incorrect because K. pneumoniae would grow well on blood agar. Answers C and D are incorrect because Nocardia grows well on BCYE but is Gram positive, as is S. pneumoniae.
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Reference: Legionella
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Board review style question #2
A 55 year old woman is admitted with pneumonia and concern for Legionnaires disease. While cultures are ongoing, what rapid test can be performed to support this diagnosis?
- Bronchoalveolar lavage (BAL) antigen
- IgM / IgG serology
- Serum antigen
- Urinary antigen
Board review style answer #2
D. Urinary antigen testing for Legionella pneumophila serogroup 1, the most common cause of legionellosis, is rapid, inexpensive, sensitive and widely available. Answers A and C are incorrect because antigen testing is not performed using other specimens such as BAL or serum. Answer B is incorrect because serology testing is not considered rapid and is generally not useful for the diagnosis of acute legionellosis.
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Reference: Legionella
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