Legionella

Background

Microbiology

• Small, fastidious Gram-negative bacillus
• Uses proteins rather than carbohydrates as an energy source
  • Requires media enriched with L-cysteine
• L. pneumophila is an facultative intracellular parasite of a number of amoebae
• Close relative of Coxiella burnetti
• Also have a quiescent state that is "viable but not cultivable"

Species

• L. pneumophila serogroup 1: most common cause (70-80%)
• L. micdadei: sometimes referred to as the "Pittsburgh pneumonia agent" or Tatlockia micdadei
• L. pneumophila serogroups 2-15
• L. dumoffi
• L. longbeachae
• L. bozemanii

Epidemiology

• Ubiquitous in water: lakes, streams, oceans
  • Warm water has higher burden of bacteria
  • Free-living water amoebae support intracellular growth of Legionella
• No person-to-person transmission (one case report)
• Most cases are sporadic, but there are also epidemics
  • Half of cases are associated with travel
  • Other risk factors include cell-mediated immunocompromise (e.g. anti-TNF-alpha)
  • Also spas, hot tubs, potting mix
• Most common strain is L. pneumophila Pontiac subtype serogroup 1 (90%)

Pathophysiology

• Inhalation or microaspiration
• Phagocytosed by alveolar macrophages
  • Replicate intracellularly, then escape and are rephagocytosed by other macrophages
• The population of bacteria increases in the lungs
  • Infiltration by neutrophils etc causes pulmonary edema

Clinical Manifestations

• Incubation period of 2 to 10 days (median 4 to 6 days); at most up to 28 days

Legionnaires' Disease

• Presents as a community-acquired or healthcare-associated pneumonia
• May have a prodrome of hours to days that involves headaches, myalgias, asthenia, and anorexia, possibly fevers
  • Diarrhea and abdominal pain
  • Cough, sometimes chest pain, sometimes productive
• Fevers with pulse-temperature dissociation, myalgias, nonproductive cough, diarrhea, confusion, hyponatremia, hypophosphatemia, and elevated liver enzymes
• Can have leukopenia, thrombocytopenia, DIC, leukocytosis, pyuria

Extrapulmonary Infections

• Rare, in immunocompromised patients or severe illness
  • Except for pleural effusions, which are common
• Can develop abscesses in brain, spleen, extrathoracic lymph nodes, and skeletal and myocardial myscles
• Case reports of endocarditis

Pontiac Fever

• Incubation period 4 hours to 3 days
• Self-limited, short febrile illness
  • Fevers, myalgias, headaches, and asthenia
  • Only diagnosed when there's an outbreak, since they're usually not sick enough to present to healthcare
  • Outbreaks associated with industrial processes using sprayed water, recreational spas, decorative water fountains, and cooling towers
• Can have cough, dyspnea, anorexia, arthralgia, and abdominal pain

Diagnosis

• Legionella urine antigen if the most widely-used test
  • Most sensitive for L. pneumophila serogroup 1, less sensitive for others
• Cultured best on buffered charcoal yeast extract (BCYE) agar is preferred
  • Colistin
  • Needs cysteine
• Stained best with Warthin-Starry or Dieterle, but stains poorly

Test	Specimens	Sensitivity	Specificity	Notes
Culture	Spurum, other lower respiratory tract secretions, lung, pleural fluid, blood, extrapulmonary tissues, fluids	20-95%	100%	Positive several days after treatment, needs special media
Antigen	Urine	60-95%	>99%	Highest sensitivity for serogroup 1, Pontiac type; positive for days to months
Immunofluorescent microscopy	Same as culture	20-50%	99%	Highest specificity with monoclonal antibody
Antibody	Paired serum (acute and convalescent)	20-70%	95-99%	Highest specificity for serogroup 1
Molecular amplification	Sputum (ideally BAL), other lower respiratory tract secretions, urine	70-95%	90-95%	Not well standardized, good performance in reference labs

Management

• First-line: Levofloxacin 750 mg PO or IV once daily or moxifloxacin 400 mg PO or IV once daily
• Alternative: azithromycin 500 mg PO or IV once daily
• Usual duration 7-10 days
• No need to treat Pontiac fever

Prevention

• https://www.cdc.gov/legionella/health-depts/index.html