Recommended Oral Antibiotic for Community-Acquired Pneumonia
For otherwise healthy adults without comorbidities, amoxicillin 1 g orally every 8 hours is the recommended first-line oral antibiotic for community-acquired pneumonia. 1, 2
Treatment Algorithm Based on Patient Risk Factors
Healthy Adults (No Comorbidities)
First-line options:
- Amoxicillin 1 g every 8 hours (strong recommendation, moderate quality evidence) 1, 2
- Doxycycline 100 mg twice daily (conditional recommendation, low quality evidence) 1
The recommendation for high-dose amoxicillin is based on demonstrated efficacy in both inpatient and outpatient CAP despite lack of coverage for atypical organisms, with a long track record of safety. 1 This regimen has proven effective even against drug-resistant Streptococcus pneumoniae. 2 Some experts recommend starting doxycycline with a 200 mg loading dose to achieve adequate serum levels more rapidly. 1
Adults with Comorbidities (Age ≥65, COPD, Diabetes, Heart Disease, Asplenia)
Combination therapy (preferred):
- Amoxicillin/clavulanate 500 mg/125 mg three times daily, OR 875 mg/125 mg twice daily, OR 2,000 mg/125 mg twice daily PLUS 1, 2
- Macrolide: Azithromycin 500 mg on day 1, then 250 mg daily OR clarithromycin 500 mg twice daily (strong recommendation, moderate quality evidence) 1, 3
- Alternative to macrolide: Doxycycline 100 mg twice daily (conditional recommendation, low quality evidence) 1
OR
Monotherapy:
- Respiratory fluoroquinolone: Levofloxacin 750 mg daily, moxifloxacin 400 mg daily, OR gemifloxacin 320 mg daily (strong recommendation, moderate quality evidence) 1, 4
The fluoroquinolone option provides convenience of monotherapy with coverage of both typical and atypical organisms, excellent oral bioavailability, and very low resistance rates in common CAP pathogens. 1 However, increasing FDA warnings regarding fluoroquinolone adverse events should be considered. 1
Critical Dosing Considerations and Pitfalls
Avoid these common errors:
Never use standard-dose amoxicillin (250-500 mg three times daily) for pneumonia, as underdosing increases treatment failure risk and promotes resistance. 2
Do not use amoxicillin monotherapy in patients with comorbidities without adding atypical coverage, as mixed infections with Mycoplasma or Chlamydophila are common. 2
Switch to a different antibiotic class if the patient received the same class within the past 3 months to reduce resistance risk. 1, 2
Avoid macrolide monotherapy in areas with pneumococcal macrolide resistance ≥25%, though amoxicillin remains effective. 2, 3
Treatment Duration
5-7 days of treatment is recommended for most cases of CAP in patients demonstrating clinical improvement. 2 Treatment should not routinely exceed 8 days in responding patients. 2 Meta-analysis of 15 randomized controlled trials comprising 2,796 subjects demonstrated no difference in clinical failure, mortality, or bacteriologic eradication between short-course (≤7 days) and extended-course (>7 days) regimens. 5
Special Populations Requiring Alternative Coverage
Do not use standard CAP regimens for:
- Suspected MRSA pneumonia - requires vancomycin or linezolid 2
- Suspected Pseudomonas aeruginosa pneumonia - requires anti-pseudomonal coverage 1, 2
These patients are uncommonly managed in the outpatient setting but require specific pathogen-directed therapy. 1
Comparative Efficacy Evidence
Research demonstrates equivalence among recommended regimens. A randomized trial of 267 outpatients showed azithromycin 1 g daily for 3 days achieved 92.6% clinical success versus 93.1% for amoxicillin-clavulanate 875/125 mg twice daily for 7 days. 6 A prospective double-blind trial of 65 hospitalized patients found doxycycline 100 mg twice daily was as efficacious as levofloxacin 500 mg daily, with significantly lower cost ($64.98 vs $122.07) and shorter length of stay (4.0 vs 5.7 days). 7