What is the recommended treatment for community-acquired pneumonia in an otherwise healthy adult?

Treatment of Community-Acquired Pneumonia in Otherwise Healthy Adults

For otherwise healthy adults with community-acquired pneumonia managed as outpatients, amoxicillin 1 gram three times daily is the preferred first-line antibiotic, with doxycycline 100 mg twice daily as an acceptable alternative. 1

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

First-line therapy:

• Amoxicillin 1 g orally three times daily (preferred based on moderate quality evidence for effectiveness against common CAP pathogens) 1
• Doxycycline 100 mg orally twice daily (acceptable alternative, conditional recommendation) 2, 1

Macrolide considerations:

• Azithromycin (500 mg day 1, then 250 mg daily) or clarithromycin (500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is documented <25% 2, 1
• In regions with high macrolide resistance (≥25%), avoid macrolide monotherapy entirely due to treatment failure risk 2, 1

Adults With Comorbidities or Recent Antibiotic Use

Comorbidities include: COPD, diabetes, chronic heart/liver/renal disease, malignancy, or antibiotic use within the past 3 months 2

Combination therapy option:

• β-lactam (amoxicillin-clavulanate 2 g twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) or doxycycline 2, 1

Fluoroquinolone monotherapy option:

• Levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily 2, 1
• Reserve fluoroquinolones for specific situations due to FDA warnings about serious adverse events and resistance concerns 1

Inpatient Treatment (Non-ICU)

Two equally effective regimens with strong recommendations:

Option 1 - Combination therapy:

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

Option 2 - Fluoroquinolone monotherapy:

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 2, 1

For penicillin-allergic patients:

• Respiratory fluoroquinolone is the preferred alternative 2

ICU Treatment (Severe CAP)

Mandatory combination therapy for all ICU patients:

Standard regimen:

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

For Pseudomonas aeruginosa risk factors (structural lung disease, recent hospitalization with IV antibiotics within 90 days, prior P. aeruginosa isolation):

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 2
• Alternative: antipseudomonal β-lactam PLUS aminoglycoside (gentamicin 5-7 mg/kg IV daily) PLUS azithromycin or respiratory fluoroquinolone 2

For MRSA risk factors (prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates):

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

Duration of Therapy

Standard duration:

• Minimum 5 days AND patient must be afebrile for 48-72 hours with no more than one sign of clinical instability before discontinuation 2, 1
• Typical duration for uncomplicated CAP: 5-7 days 2, 1

Extended duration (14-21 days) required for:

• Legionella pneumophila 2, 1
• Staphylococcus aureus 2, 1
• Gram-negative enteric bacilli 2, 1

Transition to Oral Therapy

Switch from IV to oral when ALL criteria met:

• Hemodynamically stable 2
• Clinically improving 2
• Able to ingest medications 2
• Normal gastrointestinal function 2
• Typically occurs by day 2-3 of hospitalization 1

Preferred oral step-down regimens:

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 1
• Alternative: clarithromycin 500 mg orally twice daily can substitute for azithromycin 1

Critical Timing Considerations

For hospitalized patients:

• Administer first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department 2, 1
• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1

Diagnostic Testing

For hospitalized patients:

• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy 1
• Chest radiograph not required before hospital discharge in patients with satisfactory clinical recovery 1
• Schedule clinical review at 6 weeks for all hospitalized patients 1

Critical Pitfalls to Avoid

Antibiotic selection errors:

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25% 2, 1
• Never use macrolide monotherapy for hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to resistance concerns and serious adverse events 1

Treatment duration errors:

• Avoid extending therapy beyond 7 days in responding patients without specific indications—increases antimicrobial resistance risk without improving outcomes 1

Coverage errors:

• Do not automatically escalate to broad-spectrum antibiotics based solely on comorbidities without documented risk factors for resistant organisms 1
• Only add antipseudomonal coverage when specific risk factors present (structural lung disease, recent hospitalization with IV antibiotics, prior P. aeruginosa isolation) 2
• Only add MRSA coverage when specific risk factors present (prior MRSA infection, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates) 2