What is the recommended treatment for a patient with community-acquired pneumonia (CAP)?

Community-Acquired Pneumonia Treatment

For outpatients without comorbidities, amoxicillin 1 g three times daily for 5-7 days is the preferred first-line therapy, while hospitalized non-ICU patients should receive ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily, and ICU patients require mandatory combination therapy with a β-lactam plus either azithromycin or a respiratory fluoroquinolone. 1

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line agent based on strong recommendation and moderate quality evidence 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative with conditional recommendation 1
• Macrolides (azithromycin or clarithromycin) should ONLY be used when local pneumococcal macrolide resistance is documented <25% 1, 2

Adults With Comorbidities (COPD, diabetes, heart/liver/renal disease, malignancy, or recent antibiotic use)

• Combination therapy: β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) or doxycycline 1
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) 1, 3

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong recommendations and high-quality evidence: 1

Preferred Regimen

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily 1, 4
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 1

Alternative Regimen

• Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 3
• This option is preferred for penicillin-allergic patients 1

Severe CAP Requiring ICU Admission

Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate and associated with higher mortality: 1, 5

Standard ICU Regimen

• Ceftriaxone 2 g IV daily (or cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours) PLUS azithromycin 500 mg IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 5

Special Pathogen Coverage

Add antipseudomonal coverage ONLY when these risk factors are present: 1

• Structural lung disease (bronchiectasis, cystic fibrosis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of Pseudomonas aeruginosa

Antipseudomonal regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) 1

Add MRSA coverage ONLY when these risk factors are present: 1

• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics
• Post-influenza pneumonia
• Cavitary infiltrates on imaging

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

Duration of Therapy

• Minimum of 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 1, 6, 4
• Typical duration for uncomplicated CAP: 5-7 days 1, 6
• Extended duration (14-21 days) required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 6

Transition to Oral Therapy

Switch from IV to oral antibiotics when ALL of these criteria are met: 1, 6

• Hemodynamically stable
• Clinically improving
• Afebrile for 48-72 hours
• Able to take oral medications
• Normal gastrointestinal function
• Typically achievable by day 2-3 of hospitalization 1

Oral Step-Down Options

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 1
• Amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin 500 mg orally daily 1
• Levofloxacin 750 mg orally once daily (for penicillin-allergic patients) 1, 3

Critical Timing Considerations

• Administer the first antibiotic dose IMMEDIATELY upon diagnosis, ideally in the emergency department 1, 5
• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 1, 4

Essential Diagnostic Testing

For ALL hospitalized patients, obtain BEFORE initiating antibiotics: 1

• Blood cultures (two sets from separate sites)
• Sputum Gram stain and culture (if high-quality specimen available)
• Urinary antigen testing for Legionella pneumophila serogroup 1 (in severe CAP or ICU patients)
• COVID-19 and influenza testing when these viruses are common in the community 4

Management of Treatment Failure

If no clinical improvement by day 2-3: 1, 6

• Obtain repeat chest radiograph, CRP, white blood cell count
• Consider chest CT to evaluate for complications (pleural effusion, lung abscess, central airway obstruction)
• Obtain additional microbiological specimens
• For non-severe pneumonia on amoxicillin monotherapy: Add or substitute a macrolide 6
• For non-severe pneumonia on combination therapy: Switch to respiratory fluoroquinolone 6
• For severe pneumonia not responding to combination therapy: Consider adding rifampicin 6

Critical Pitfalls to Avoid

• NEVER use macrolide monotherapy in hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• NEVER use macrolides in areas where pneumococcal macrolide resistance exceeds 25%—leads to treatment failure 1, 2
• NEVER delay antibiotic administration—each hour of delay increases mortality 1, 5, 4
• NEVER add antipseudomonal or MRSA coverage without documented risk factors—promotes resistance without benefit 1
• NEVER extend therapy beyond 7-8 days in responding patients without specific indications—increases antimicrobial resistance risk 1