Clinical Setting

• Community or hospital-acquired pneumonia, extrapulmonary infections (e.g., endocarditis) occur but are rare
• Despite cough, patients with pneumonia may produce small amounts of mucoid non-purulent sputum
• Risk factors: Immunocompromised patient, smoking, co-morbidities.
• Associated clinical findings with pneumonia (although nonspecific):
  
  • Diarrhea, other gastrointestinal symptoms
  • Confusion
  • Relative bradycardia
  • Hyponatremia
  • Elevated hepatic enzymes
  • Elevated BUN and creatinine
  • Elevated ferritin levels. Range of peak levels: 591-5990 (Clin Infect Dis 46:1789, 2008)

Diagnosis

• Culture (requires selective media) or PCR: detects multiple serotypes.
• Antigen assay, direct fluorescent antibody, or serology detects L. pneumophila serotype 1 strains only (for review of diagnostics see Clin Microbiol Rev 28:95, 2015).

Classification

• Gram negative bacilli
• Legionella pneumophila (60-80% of cases)
• Legionella (tatlockia)   micdadei
• Legionella wadsworthii
• ~40 species identified, most rarely associated with human disease

Primary Regimens

• Pneumonia
  • Levofloxacin 750 mg IV/po q24h or Moxifloxacin 400 mg IV/po q24 
  • Azithromycin 500 mg IV/po q24h 
  • No proven benefit of Rifampin combination therapy (and drug interactions are a major issue in many patients) or combination of Azithromycin + fluoroquinolone
• Endocarditis: above (see Comments)

Alternative Regimens

• Pneumonia
  • Clarithromycin 500 mg IV/po q12h or Erythromycin 500 mg to 1 gm q6h IV/po q6h (less well tolerated and may be less effective than primary regimens) 
  • Doxycycline 100 mg IV/po q12h
• Endocarditis (see Comments)
  
  • Doxycycline 200 mg bid po/IV
  • Erythromycin 500 mg po/IV q6h + Rifampin 600-1200 mg po in 2 or more divided doses
  • Ciprofloxacin at 400 mg IV q12h or 500 mg po bid

Antimicrobial Stewardship

• Duration of therapy.
  • 7-10 days of IV/po therapy depending on clinical response is appropriate for immunocompetent patients with legionella pneumonia.
  • 14-21 days of therapy with IV/po therapy depending on clinical response is recommended for immunocompromised patients.
  • Duration of therapy not well defined, but prolonged therapy, up to 5 months, has been used

Comments

• For endocarditis
  • Advise microbiology laboratory when considering the diagnosis of Legionella spp. endocarditis as it is possible to isolate the organism in blood culture media with special handling..
  • Infectious Diseases consultation recommended
  • Several Legionella spp have been reported as causes of endocarditis.
  • Most patients reported in the literature have undergone valve replacement in addition to medical therapy.
  • Treatment recommendations based on anecdotal case reports.
  • References: J Infect 51:e256, 2005,  Clin Micro Rev 2001; 14:177, Circulation. 2015;132:1435-1486.
• Macrolides and fluoroquinolones are probably equally effective (Clin Infect Dis 2021;72:1979).
  • Most fluoroquinolones are active in vitro (Gemifloxacin, Moxifloxacin).
• TMP-SMP also probably effective but less data to support its efficacy
• Reference on diagnosis and treatment: Infect Dis Ther. 2022; 11:973-986.