Outpatient Community-Acquired Pneumonia: Antibiotic Recommendations
For Otherwise Healthy Patients Without Comorbidities
For healthy outpatients without comorbidities, prescribe amoxicillin 1 gram three times daily as first-line therapy, or alternatively doxycycline 100 mg twice daily. 1
First-Line Options (in order of preference):
Amoxicillin 1 gram orally three times daily (strong recommendation, moderate quality evidence) 1
Doxycycline 100 mg orally twice daily (conditional recommendation, low quality evidence) 1, 3
Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) ONLY if local pneumococcal macrolide resistance is <25% (conditional recommendation, moderate quality evidence) 1
Critical Pitfalls to Avoid:
- Do NOT use macrolides as monotherapy in areas with pneumococcal macrolide resistance ≥25% 1
- Do NOT use doxycycline if patient had recent doxycycline exposure due to resistance risk 3
- Avoid fluoroquinolones in otherwise healthy patients - reserve for patients with comorbidities 1
- Be aware of photosensitivity with doxycycline in sunny climates 3
For Patients With Comorbidities
For outpatients with comorbidities (chronic heart/lung/liver/renal disease, diabetes, alcoholism, malignancy, asplenia), prescribe either combination therapy with a beta-lactam plus macrolide/doxycycline, OR monotherapy with a respiratory fluoroquinolone. 1
Combination Therapy Options (strong recommendation for beta-lactam + macrolide):
Beta-lactam component (choose one):
- Amoxicillin/clavulanate 500/125 mg three times daily, OR
- Amoxicillin/clavulanate 875/125 mg twice daily, OR
- Amoxicillin/clavulanate 2000/125 mg twice daily, OR
- Cefpodoxime 200 mg twice daily, OR
- Cefuroxime 500 mg twice daily 1
PLUS one of the following:
- Azithromycin 500 mg day 1, then 250 mg daily (strong recommendation, moderate quality evidence) 1
- Clarithromycin 500 mg twice daily or extended-release 1000 mg daily (strong recommendation, moderate quality evidence) 1
- Doxycycline 100 mg twice daily (conditional recommendation, low quality evidence) 1
Monotherapy Option:
Respiratory fluoroquinolone (strong recommendation, moderate quality evidence) 1:
- Levofloxacin 750 mg daily, OR
- Moxifloxacin 400 mg daily, OR
- Gemifloxacin 320 mg daily
The fluoroquinolones demonstrate >90% clinical success rates for S. pneumoniae including multidrug-resistant strains 5, 2
Evidence Quality and Rationale
The 2019 ATS/IDSA guidelines acknowledge that RCTs show no superiority of one regimen over another for mortality or treatment failure, as these outcomes are rare in outpatients 1. The recommendations are based on:
- Inpatient CAP studies (considered applicable since outpatients have lower severity) 1
- Antimicrobial resistance surveillance data 1
- Safety profiles and adverse event data 1
- Real-world observational studies 6, 7
Key consideration: Despite guideline recommendations for broad-spectrum therapy in patients with comorbidities, real-world data from 2008-2019 showed declining use of broad-spectrum antibiotics, with 44% of comorbid patients receiving recommended broad-spectrum therapy 8. This suggests potential undertreatment in higher-risk populations.
Treatment Duration
- Standard duration: 5-7 days for uncomplicated cases 3
- Levofloxacin 750 mg daily for 5 days is FDA-approved and equivalent to 10-day courses 5
- Real-world practice shows 10-day courses remain most common, representing potential overtreatment 8
Special Populations and Modifications
If Penicillin Allergy:
- Use doxycycline 100 mg twice daily, OR
- Respiratory fluoroquinolone, OR
- Macrolide (only if local resistance <25%) 1
If Recent Antibiotic Exposure:
- Select a different antibiotic class to avoid resistance 3
- This is particularly important for patients who received antibiotics in the prior 90 days