What antibiotics are used to treat community-acquired pneumonia (CAP)?

Antibiotics Used in Community-Acquired Pneumonia (CAP)

For healthy outpatients without comorbidities, amoxicillin 1 g three times daily is the first-line antibiotic choice, with doxycycline or macrolides as alternatives only in areas with pneumococcal macrolide resistance <25%. 1, 2, 3

Outpatient Treatment

Healthy Adults Without Comorbidities

• First-line: Amoxicillin 1 g three times daily (strong recommendation, moderate quality evidence) 1, 2
• Alternative options:
  • Doxycycline 100 mg twice daily (conditional recommendation, low quality evidence) 1, 2
  • Macrolides (azithromycin 500 mg on day 1, then 250 mg daily OR clarithromycin 500 mg twice daily) ONLY in areas with pneumococcal macrolide resistance <25% 1, 3

Adults With Comorbidities or Risk Factors

• Combination therapy (preferred):
  • Amoxicillin/clavulanate (500/125 mg three times daily, 875/125 mg twice daily, or 2000/125 mg twice daily) OR cephalosporin (cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily) PLUS macrolide (azithromycin or clarithromycin) or doxycycline 100 mg twice daily 1, 2
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin, or gemifloxacin) 4, 1

Critical caveat: Recent antibiotic use within 3 months mandates selection from a different antibiotic class to avoid resistance 2, 3. In regions with high macrolide resistance (>25%), avoid macrolide monotherapy even in healthy patients 4, 3.

Inpatient Non-ICU Treatment

Preferred Regimen

• β-lactam PLUS macrolide (strong recommendation, level I evidence):
  • β-lactam options: Ceftriaxone, cefotaxime, ampicillin/sulbactam, or ceftaroline 4, 1, 2
  • Macrolide options: Azithromycin or clarithromycin 4, 1
  • Doxycycline may substitute for macrolide (level III evidence) 4

Alternative Regimen

• Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg daily, moxifloxacin, or gemifloxacin (strong recommendation, level I evidence) 4, 1, 2

Important consideration: Ertapenem is an acceptable β-lactam alternative for patients with risk factors for gram-negative pathogens (excluding Pseudomonas aeruginosa) 4.

Severe CAP Requiring ICU Care

Without Pseudomonas Risk Factors

• Non-antipseudomonal β-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) PLUS either:
  • Azithromycin (level II evidence) OR
  • Respiratory fluoroquinolone (level I evidence) 4, 1, 2

With Pseudomonas Risk Factors

Risk factors include: Severe structural lung disease (bronchiectasis), recent antibiotic therapy, or recent hospitalization/ICU stay 2.

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS either:
  • Ciprofloxacin or levofloxacin 750 mg OR
  • Aminoglycoside (gentamicin, tobramycin, or amikacin) PLUS azithromycin OR
  • Aminoglycoside PLUS antipneumococcal fluoroquinolone 4, 1, 2

For penicillin-allergic patients with Pseudomonas risk: Aztreonam plus levofloxacin or aztreonam plus moxifloxacin, with or without aminoglycoside 2.

Special Pathogen Coverage

MRSA Risk Factors

• Add vancomycin or linezolid to the regimen 4, 1, 2
• Obtain cultures and nasal PCR to allow de-escalation 1, 2

Suspected Legionella

• Respiratory fluoroquinolone (levofloxacin preferred) OR macrolide (azithromycin preferred) ± rifampin 1

Mycoplasma or Chlamydophila

• Macrolide, doxycycline, or respiratory fluoroquinolone 1

Treatment Duration and Timing

• Duration: Generally 5-7 days for responding patients 1, 2
• Patients should be afebrile for 48-72 hours before discontinuing antibiotics 2
• Procalcitonin levels may guide shorter treatment duration 1, 2
• Timing: For hospitalized patients admitted through the emergency department, administer first antibiotic dose while still in the ED 4
• Antibiotic administration within 8 hours of hospital arrival reduces 30-day mortality by 20-30% in patients ≥65 years 4

Critical Pitfalls to Avoid

Macrolide resistance: 20-30% of S. pneumoniae isolates demonstrate macrolide resistance; avoid macrolide monotherapy in areas with resistance >25% 2, 3.

Fluoroquinolone overuse: Reserve fluoroquinolones for appropriate patients to prevent resistance development; recent fluoroquinolone use mandates selection of non-fluoroquinolone regimen 2.

Inadequate pathogen coverage: S. pneumoniae remains the most common causative pathogen across all disease severities; ensure empiric coverage 2.

Delayed antibiotic administration: Prompt initiation is essential as delays increase mortality 2.

Pseudomonas coverage: When P. aeruginosa is documented or presumptive, combination therapy with an anti-pseudomonal β-lactam is mandatory 4.