Treatment of Outpatient Community-Acquired Pneumonia
For otherwise healthy adults without comorbidities, amoxicillin 1 gram three times daily for 5-7 days is the first-line treatment, with doxycycline 100 mg twice daily as the preferred alternative. 1, 2
Treatment Algorithm Based on Patient Characteristics
Healthy Adults Without Comorbidities
Amoxicillin 1 gram orally three times daily for 5-7 days is the strongest recommendation (strong recommendation, moderate quality evidence) as it provides optimal coverage against Streptococcus pneumoniae, which accounts for approximately 48% of identified CAP cases and is the most common cause of lethal community-acquired pneumonia. 1, 2, 3
Doxycycline 100 mg orally twice daily for 5-7 days is the preferred alternative (conditional recommendation, low quality evidence), with the ATS/IDSA suggesting a 200 mg loading dose on day 1 to achieve adequate serum levels more rapidly. 1, 2
Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for days 2-5) should ONLY be used if local pneumococcal macrolide resistance is documented to be less than 25% (conditional recommendation, moderate quality evidence). 1, 2, 4
Adults With Comorbidities
Comorbidities include diabetes, chronic heart disease, chronic liver disease, chronic renal disease, or recent antibiotic use within 90 days. 1, 2
Combination therapy is first-line: amoxicillin/clavulanate (875 mg/125 mg twice daily OR 2000 mg/125 mg twice daily) PLUS a macrolide (azithromycin or clarithromycin) OR doxycycline 100 mg twice daily for 5-7 days (strong recommendation, moderate quality evidence). 1, 2
Respiratory fluoroquinolone monotherapy is an equally strong alternative: levofloxacin 750 mg once daily for 5 days OR moxifloxacin 400 mg once daily for 5-7 days (strong recommendation, moderate quality evidence). 1, 2
Fluoroquinolones are active against more than 98% of S. pneumoniae strains, including penicillin-resistant isolates, but should be reserved due to risks of tendinopathy, peripheral neuropathy, and CNS effects. 2, 4
Critical Decision Points and Common Pitfalls
When NOT to Use Certain Antibiotics
Never use macrolide monotherapy in patients with any comorbidities, areas where pneumococcal macrolide resistance is ≥25%, patients with recent antibiotic use, or patients requiring hospitalization. 1, 2
Never use doxycycline as monotherapy in patients with cardiopulmonary disease or other modifying factors—these patients require combination therapy with a β-lactam plus doxycycline. 1
Do not use doxycycline as monotherapy if risk factors for drug-resistant S. pneumoniae are present: age ≥65, recent antibiotic use within 3 months, immunosuppression, or multiple comorbidities. 1
Antibiotic Class Selection Strategy
If a patient has had recent exposure to any antibiotic class within 90 days, select a different antibiotic class to reduce risk of bacterial resistance. 1, 2
Photosensitivity is a potential side effect of doxycycline that may limit its use in certain geographic areas with high sun exposure. 1
Treatment Duration
Standard treatment duration is 5-7 days for most antibiotics, with clinical trials demonstrating no difference in clinical failure rates between short-course (≤7 days) and extended-course (>7 days) regimens. 1, 2, 5
Extend treatment to 14-21 days ONLY if: Legionella pneumophila is suspected or confirmed, Staphylococcus aureus is identified, or gram-negative enteric bacilli are isolated. 1, 2
Evidence Quality and Guideline Strength
The 2019 ATS/IDSA guidelines (reflected in the 2025 Praxis summaries) represent the most current high-quality evidence, acknowledging that randomized controlled trials show no superiority of one regimen over another for mortality or treatment failure in outpatients, as these outcomes are rare in this population. 1, 2
The recommendation for amoxicillin as first-line therapy is based on its excellent activity against 90-95% of pneumococcal strains at high doses, superior safety profile, and narrow spectrum that minimizes collateral damage to normal flora. 2
Doxycycline provides broad-spectrum coverage including atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella species) and has demonstrated comparable efficacy to fluoroquinolones in hospitalized patients at significantly lower cost, though the evidence quality for outpatient monotherapy is lower. 1, 2
When to Hospitalize
Patients should be hospitalized rather than treated as outpatients if they have: moderate to severe illness, cystic fibrosis, nosocomial acquisition, known or suspected bacteremia, requirement for hospitalization, elderly or debilitated status, or significant underlying health problems including immunodeficiency or functional asplenia. 4