What are the recommended antibiotics for community-acquired pneumonia?

Recommended Antibiotics for Community-Acquired Pneumonia

For outpatient CAP without comorbidities, use amoxicillin 1g three times daily as first-line therapy; for patients with comorbidities or requiring hospitalization, use either a beta-lactam (ceftriaxone 1-2g daily) plus azithromycin 500mg daily, or respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily or moxifloxacin 400mg daily). 1, 2

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

• Amoxicillin 1g orally three times daily is the preferred first-line agent, providing excellent coverage against Streptococcus pneumoniae and other common bacterial pathogens 2
• Doxycycline 100mg orally twice daily serves as an acceptable alternative for patients with penicillin allergy or intolerance 1, 2
• Macrolides (azithromycin 500mg day 1, then 250mg daily; or clarithromycin 500mg twice daily) should only be used in regions where pneumococcal macrolide resistance is <25% due to increasing resistance patterns 1, 2

Adults With Comorbidities (COPD, diabetes, heart disease, renal disease)

• Combination therapy with beta-lactam plus macrolide: amoxicillin-clavulanate 2g twice daily or cefpodoxime plus azithromycin 500mg daily 1, 2
• Alternative monotherapy with respiratory fluoroquinolone: levofloxacin 750mg daily, moxifloxacin 400mg daily, or gemifloxacin 320mg daily 1, 2

Inpatient Non-ICU Treatment

Two equally effective regimens exist with strong evidence:

Combination Therapy (Preferred by most guidelines)

• Ceftriaxone 1-2g IV daily plus azithromycin 500mg IV/oral daily provides comprehensive coverage for typical and atypical pathogens 1, 2, 3
• Alternative beta-lactams include cefotaxime 1-2g IV every 8 hours or ampicillin-sulbactam 3g IV every 6 hours 1, 2
• Administer the first antibiotic dose in the emergency department before admission to reduce mortality 1, 2

Fluoroquinolone Monotherapy

• Levofloxacin 750mg IV/oral daily or moxifloxacin 400mg IV/oral daily as single-agent therapy 1, 2, 4
• This regimen demonstrated 90.9% clinical success in hospitalized patients 4
• Particularly useful for penicillin-allergic patients 2

ICU-Level Severe CAP

Combination therapy is mandatory for all ICU patients:

• Beta-lactam (ceftriaxone 2g IV daily, cefotaxime 1-2g IV every 8 hours, or ampicillin-sulbactam 3g IV every 6 hours) PLUS either azithromycin 500mg IV daily OR respiratory fluoroquinolone (levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily) 1, 2
• This dual coverage addresses both typical bacterial pathogens and atypical organisms with strong recommendation 1, 2

Special Populations Requiring Broader Coverage

Pseudomonas Risk Factors (structural lung disease, recent hospitalization with IV antibiotics, prior P. aeruginosa isolation)

• Antipseudomonal beta-lactam (piperacillin-tazobactam 4.5g IV every 6 hours, cefepime 2g IV every 8 hours, imipenem 500mg IV every 6 hours, or meropenem 1g IV every 8 hours) PLUS ciprofloxacin 400mg IV every 8 hours OR levofloxacin 750mg IV daily 1, 2
• Alternative: antipseudomonal beta-lactam plus aminoglycoside (gentamicin 5-7mg/kg IV daily) plus azithromycin 1, 2

MRSA Risk Factors (prior MRSA infection, recent hospitalization with IV antibiotics, cavitary infiltrates, post-influenza pneumonia)

• Add vancomycin 15mg/kg IV every 8-12 hours (target trough 15-20mg/mL) OR linezolid 600mg IV every 12 hours to the base regimen 1, 2

Duration and Transition Strategy

• Minimum 5 days of therapy with clinical stability criteria met: afebrile for 48-72 hours, hemodynamically stable, improving clinically, able to take oral medications 1, 2
• Standard duration is 5-7 days for uncomplicated CAP 1, 2
• Extend to 14-21 days for Legionella, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2
• Transition from IV to oral when hemodynamically stable, clinically improving, and able to ingest medications, typically by day 2-3 1, 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in regions with >25% pneumococcal macrolide resistance or in patients with comorbidities, as treatment failure rates increase significantly 1, 2
• Avoid delayed antibiotic administration in hospitalized patients—the first dose should be given in the emergency department to reduce mortality 1, 2
• Do not automatically escalate to broad-spectrum antibiotics (carbapenems, antipseudomonal agents) without documented risk factors for resistant organisms 1, 2
• Avoid fluoroquinolone overuse in patients without comorbidities or recent antibiotic exposure to prevent resistance development 1, 2
• Do not extend therapy beyond 7 days in responding patients without specific indications, as this increases resistance risk 2
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow targeted de-escalation 1, 2

Penicillin-Allergic Patients

• Outpatient: doxycycline 100mg twice daily or respiratory fluoroquinolone 1, 2
• Inpatient non-ICU: respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily or moxifloxacin 400mg daily) 2
• ICU: respiratory fluoroquinolone plus aztreonam 2g IV every 8 hours 2