What is the appropriate treatment for a patient with suspected Mycoplasma (Mycoplasma pneumoniae) or Legionnaires' (Legionella pneumonia) disease?

Treatment for Suspected Mycoplasma or Legionella Pneumonia

For suspected Mycoplasma pneumoniae or Legionella pneumophila pneumonia, treat empirically with either a macrolide (azithromycin preferred) or a respiratory fluoroquinolone (levofloxacin), with fluoroquinolones showing superior outcomes in severe Legionella disease. 1, 2

Treatment Selection Based on Severity

Outpatient/Non-Hospitalized Patients

• First-line options include: 1

  • Azithromycin 500 mg PO on day 1, then 250 mg daily for 4 days (total 5 days) 2
  • Levofloxacin 750 mg PO daily 2
  • Clarithromycin 500 mg PO twice daily 1
  • Doxycycline 100 mg PO twice daily 1
  • Erythromycin 500 mg PO four times daily 1

• Azithromycin is preferred due to once-daily dosing, excellent tissue penetration, and superior tolerability compared to erythromycin 3, 4, 5

Hospitalized Ward Patients (Non-ICU)

• Combination therapy is recommended: 1

  • β-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) PLUS azithromycin 1
  • OR respiratory fluoroquinolone alone (levofloxacin, moxifloxacin) 1

• For confirmed Legionella in hospitalized patients, preferred regimens are: 1, 2

  • Azithromycin 1000 mg IV on day 1, then 500 mg IV/PO daily 2
  • Levofloxacin 750 mg IV/PO daily 2
  • Moxifloxacin 400 mg IV/PO daily 2

ICU/Severe Pneumonia

• Mandatory combination therapy: 1

  • β-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) PLUS either azithromycin (level II evidence) or fluoroquinolone (level I evidence) 1

• For severe Legionella disease, IV fluoroquinolones are preferred over macrolides due to more rapid clinical response and fewer complications 2

• Fluoroquinolone monotherapy is NOT established for severe CAP and should be avoided in ICU patients until pathogen identification 1

Duration of Treatment

Mycoplasma pneumoniae

• 10-14 days of therapy is recommended for immunocompetent patients 1
• Shorter courses (5 days) with azithromycin may be effective due to prolonged tissue half-life 1, 3, 4

Legionella pneumophila

• Standard duration: 7-10 days for immunocompetent patients 2
• Immunocompromised patients require 14-21 days (including those on chronic corticosteroids) 1, 2
• Treatment should be initiated as rapidly as possible, as delay increases mortality 1, 2

Key Clinical Considerations

Diagnostic Testing

• For Legionella, obtain: 1, 2

  • Urinary antigen assay (detects 80-95% of L. pneumophila serogroup 1) 1, 2
  • Respiratory culture on selective media 1

• Testing is indicated for: 1

  • Enigmatic pneumonia requiring ICU admission 1
  • Failure to respond to β-lactam therapy 1
  • Epidemiologic risk factors (recent travel, spa exposure, plumbing changes) 1

• For Mycoplasma, diagnosis requires: 6

  • Combination of serology AND PCR to confirm true infection 6
  • Serology alone has poor sensitivity/specificity 6

Fluoroquinolones vs. Macrolides for Legionella

• Fluoroquinolones demonstrate: 2

  • More rapid defervescence 2
  • Fewer complications 2
  • Shorter hospital stays 2

• Consider IV fluoroquinolones first-line for: 2

  • Severe disease 2
  • Immunocompromised hosts 2

Common Pitfalls and Caveats

Critical Warnings

• β-lactam antibiotics are completely ineffective against both Mycoplasma and Legionella and should never be used as monotherapy when these pathogens are suspected 2

• Do not rely on clinical features alone to distinguish Legionella from other pneumonias—high fever, hyponatremia, CNS manifestations, and elevated LDH are suggestive but not diagnostic 1

• Macrolide resistance is increasing in some regions, which may affect treatment efficacy for Mycoplasma 2

• For severe pneumonia, always start with IV therapy before transitioning to oral agents 2

• Azithromycin should NOT be used in patients with: 7

  • Moderate to severe illness requiring hospitalization 7
  • Known or suspected bacteremia 7
  • Significant underlying conditions (cystic fibrosis, immunodeficiency, functional asplenia) 7
  • Risk factors for QT prolongation 7

Treatment Adjustments

• If blood cultures subsequently identify S. pneumoniae without evidence of co-pathogen, consider switching from combination to single-agent therapy based on individual factors (age, comorbidities, clinical response) 1

• Treat empirically when epidemiologic evidence suggests Legionella, even with negative diagnostic tests 1

• Re-evaluate patients who remain febrile or unwell 48-72 hours after starting therapy 1