What is the recommended antibiotic treatment for community-acquired pneumonia (CAP)?

Antibiotic Treatment for Community-Acquired Pneumonia

For community-acquired pneumonia (CAP), the recommended first-line treatment is either a β-lactam plus a macrolide combination or a respiratory fluoroquinolone monotherapy, with specific regimens determined by illness severity and treatment setting. 1

Treatment Algorithm Based on Setting and Severity

Outpatient Treatment (Mild CAP)

• Previously healthy patients without recent antibiotic use:

  • First choice: Macrolide (azithromycin 500mg on day 1, then 250mg daily for days 2-5) 2
  • Alternative: Doxycycline 100mg twice daily 1

• Patients with comorbidities or recent antibiotic use:

  • First choice: Respiratory fluoroquinolone (levofloxacin 750mg daily or moxifloxacin 400mg daily) 1
  • Alternative: High-dose amoxicillin (1g three times daily) or amoxicillin-clavulanate (2g twice daily) plus a macrolide 1

Inpatient Treatment (Non-ICU)

• First choice:
  • β-lactam (ceftriaxone 1-2g daily, cefotaxime 1-2g every 8h, ampicillin 1-2g every 6h, or ampicillin-sulbactam 1.5-3g every 6h) plus a macrolide (azithromycin 500mg daily) 1
  • Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily or moxifloxacin 400mg daily) 1

Severe CAP (ICU Treatment)

• Without risk for Pseudomonas or MRSA:

  • β-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) plus either azithromycin or a respiratory fluoroquinolone 1

• With risk for Pseudomonas:

  • Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either:
    • Ciprofloxacin or levofloxacin (750mg), or
    • An aminoglycoside plus azithromycin or a respiratory fluoroquinolone 1

• With risk for MRSA:

  • Add vancomycin or linezolid to the regimen 1

Duration of Therapy

• Standard CAP: 5-7 days for uncomplicated cases 3, 4
• Severe CAP: 7-10 days 1, 3
• Atypical pathogens: 10-14 days 3
• Legionella infection: 14-21 days 3

Evidence Quality and Considerations

The recommendations for combination therapy with a β-lactam plus macrolide or fluoroquinolone monotherapy are supported by high-quality evidence from the American Thoracic Society and Infectious Diseases Society of America guidelines 1. These regimens have shown superior outcomes compared to β-lactam monotherapy in multiple studies 4.

A systematic review found that combination therapy with β-lactam plus macrolide or fluoroquinolone monotherapy was associated with reduced mortality compared to β-lactam monotherapy alone 1. However, it's important to note that some studies suggest comparable outcomes between ampicillin and ceftriaxone (both with added macrolides) for hospitalized CAP patients, with ampicillin showing lower rates of Clostridioides difficile infection 5.

Important Clinical Considerations

• Antibiotic resistance: If a patient has received antibiotics from one class in the past 3 months, choose an agent from a different class due to increased risk of resistance 1

• Macrolide resistance: In regions with high rates (>25%) of macrolide-resistant S. pneumoniae, avoid macrolide monotherapy 1

• Fluoroquinolone stewardship: Reserve newer fluoroquinolones for patients with treatment failure on other regimens, allergies to alternative agents, or documented highly resistant pneumococci 6

• Timing of first dose: For hospitalized patients, administer the first antibiotic dose while still in the emergency department 1

• Treatment assessment: Evaluate clinical response within 48-72 hours; consider treatment failure if no improvement is observed within 72 hours 3

• IV to oral switch: Transition to oral therapy when clinically stable (afebrile for 24 hours with improving symptoms) 3

The evidence strongly supports that appropriate antibiotic selection based on patient factors, setting, and severity significantly impacts morbidity and mortality in CAP. While newer agents like lefamulin and omadacycline are being studied, they require further validation before becoming first-line recommendations 1.