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

Treatment of Community-Acquired Pneumonia in Healthy Adults

For an otherwise healthy adult with community-acquired pneumonia treated as an outpatient, amoxicillin 1 gram orally three times daily for 5-7 days is the preferred first-line therapy. 1

Outpatient Treatment for Healthy Adults Without Comorbidities

Primary recommendation:

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line agent based on moderate quality evidence supporting effectiveness against common CAP pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis 1

Alternative options:

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries a conditional recommendation with lower quality evidence 1
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented to be <25% 1, 2

Critical Pitfall to Avoid

Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and breakthrough pneumococcal bacteremia occurs significantly more frequently with resistant strains 1. The American Thoracic Society downgraded macrolide monotherapy from a strong to a conditional recommendation based on local resistance patterns 1.

Outpatient Treatment for Adults With Comorbidities

If the patient has comorbidities (COPD, diabetes, chronic heart/liver/renal disease, malignancy) or recent antibiotic use within 90 days, escalate to combination therapy 1:

Preferred combination regimens:

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 for total duration of 5-7 days 1
• Alternative β-lactams include cefpodoxime or cefuroxime combined with macrolide or doxycycline 1

Alternative monotherapy:

• Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) 1, 3
• However, fluoroquinolone use should be discouraged in uncomplicated cases due to FDA warnings about serious adverse events and resistance concerns 1

Inpatient Treatment for Non-ICU Patients

For hospitalized patients without ICU-level severity, two equally effective regimens exist with strong recommendations and high-quality evidence 1:

Option 1: β-lactam plus macrolide combination

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

Option 2: Respiratory fluoroquinolone monotherapy

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 3
• Systematic reviews demonstrate fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations 1

For penicillin-allergic patients: Respiratory fluoroquinolone is the preferred alternative 1

Critical Timing Consideration

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

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease 1, 2:

Preferred 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 1, 2
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2

Special Pathogen Coverage

Add antipseudomonal coverage if the patient has 1:

• Structural lung disease (bronchiectasis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of P. aeruginosa

Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin or levofloxacin PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 1

Add MRSA coverage if the patient has 1, 2:

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

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

Treat for a minimum of 5 days and until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability 1, 2:

• Typical duration for uncomplicated CAP: 5-7 days 1
• Extended duration (14-21 days) required for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1

Transition from IV to Oral Therapy

Switch from IV to oral antibiotics when the patient is 1:

• Hemodynamically stable
• Clinically improving
• Able to take oral medications
• Has normal GI function
• Typically by day 2-3 of hospitalization

Oral step-down options:

• Amoxicillin 1 g orally three times daily (if initially on ceftriaxone) 1
• Continue azithromycin 500 mg orally daily if combination therapy was used 1

Diagnostic Testing

For all hospitalized patients, obtain blood cultures and sputum Gram stain/culture before initiating antibiotics to allow pathogen-directed therapy and potential de-escalation 1.

Key Evidence Supporting Recommendations

The 2019 IDSA/ATS guidelines provide strong recommendations with high-quality evidence for these regimens 1. Levofloxacin demonstrates effectiveness against drug-resistant S. pneumoniae with clinical and bacteriological success rates of 95% for multi-drug resistant strains 3. Among otherwise healthy CAP patients, narrow-spectrum regimens (macrolide or doxycycline) confer lower risk of adverse drug events compared to broad-spectrum antibiotics 4.