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

Recommended Antibiotic Regimen for Community-Acquired Pneumonia

For outpatient treatment of community-acquired pneumonia (CAP), amoxicillin 1 g three times daily is the preferred first-line therapy for healthy adults without comorbidities, while combination therapy with a β-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone is recommended for patients with comorbidities. 1

Outpatient Treatment

Patients Without Comorbidities

• Amoxicillin 1 g every 8 hours (strong recommendation, moderate quality evidence) 2, 1
• Doxycycline 100 mg twice daily (conditional recommendation, low quality evidence) 2, 1
• Macrolides (azithromycin 500 mg on first day then 250 mg daily, or clarithromycin 500 mg twice daily or extended-release 1,000 mg once daily) should only be used in areas where pneumococcal resistance to macrolides is <25% 2, 1

Patients With Comorbidities

• Combination therapy: β-lactam (amoxicillin/clavulanate, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline (strong recommendation, moderate quality evidence) 2, 1
• Monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) (strong recommendation, moderate quality evidence) 2, 1

Inpatient Treatment (Non-ICU)

• β-lactam (ampicillin + sulbactam, cefotaxime, ceftriaxone, or ceftaroline) plus a macrolide (strong recommendation, high quality evidence) 1
• Respiratory fluoroquinolone monotherapy (levofloxacin or moxifloxacin) (strong recommendation, high quality evidence) 1
• β-lactam plus doxycycline as an alternative (conditional recommendation, low quality evidence) 1

Inpatient Treatment (ICU)

• β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin or a respiratory fluoroquinolone (strong recommendation) 1
• For penicillin-allergic patients: respiratory fluoroquinolone plus aztreonam 1

Duration of Therapy

• Standard duration of 5-7 days for uncomplicated CAP 1
• Shorter course, high-dose regimens have shown efficacy, such as levofloxacin 750 mg daily for 5 days 3, 4

Special Considerations

Antibiotic Selection Based on Previous Exposure

• Patients who have received antibiotics in the previous 3 months should be treated with an agent from a different class to avoid developing resistance 1

Specific Pathogens

• For suspected Pseudomonas infection: antipseudomonal β-lactam plus either ciprofloxacin/levofloxacin or an aminoglycoside 1
• For suspected community-acquired MRSA: add vancomycin or linezolid to the regimen 1

Route of Administration

• Oral therapy is appropriate for non-severe CAP in outpatients 2
• For hospitalized patients, administer the first antibiotic dose while still in the emergency department 1
• Switch from IV to oral therapy when patients are hemodynamically stable, clinically improving, able to take oral medications, and have normal GI function 1

Clinical Pitfalls to Avoid

• Avoid macrolide monotherapy in areas with high resistance rates (>25%) to prevent treatment failure 1
• Avoid delayed antibiotic administration in hospitalized patients as it may increase mortality risk 1
• Fluoroquinolones should be used judiciously due to concerns about developing resistance and adverse effects, including cardiac arrhythmias and tendinopathy 2, 1
• Doxycycline has shown comparable efficacy to levofloxacin in hospitalized patients with CAP at a significantly lower cost, making it a viable alternative in appropriate patients 5
• For patients with severe CAP not responding to combination antibiotic treatment, consider adding rifampicin 2

Evidence Comparison

The most recent guidelines from the American Thoracic Society and Infectious Diseases Society of America (2019) recommend amoxicillin as first-line therapy for healthy outpatients 2, 1, which differs from earlier North American guidelines that favored macrolides 2. This shift reflects growing concerns about pneumococcal resistance to macrolides 1.

European guidelines, including the British Thoracic Society, have historically preferred aminopenicillins as first-line therapy 2, which aligns with current recommendations. This approach minimizes fluoroquinolone use, reducing the risk of developing resistance 2.

Clinical trials have demonstrated that high-dose, short-course levofloxacin therapy (750 mg for 5 days) is as effective as the traditional 500 mg for 10 days regimen, potentially improving compliance and reducing total antibiotic usage 3, 4.