What are the recommended oral antibiotics for community-acquired pneumonia (CAP)?

Oral Antibiotics for Community-Acquired Pneumonia

For previously healthy outpatients without comorbidities, amoxicillin 1 gram three times daily for 5-7 days is the first-line oral antibiotic, with doxycycline 100 mg twice daily as the preferred alternative. 1, 2

Treatment Algorithm Based on Patient Risk Stratification

Healthy Adults Without Comorbidities (Outpatient)

First-line therapy:

• Amoxicillin 1 g orally three times daily for 5-7 days (strong recommendation, moderate quality evidence) 1, 2
• This targets Streptococcus pneumoniae, which accounts for 48% of identified CAP cases and remains susceptible in 90-95% of strains at high doses 1

Alternative options:

• Doxycycline 100 mg orally twice daily for 5-7 days (conditional recommendation, low quality evidence) 1, 2
• Doxycycline provides broad-spectrum coverage including atypical organisms and demonstrates comparable efficacy to fluoroquinolones at significantly lower cost 1, 3

Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for days 2-5; or clarithromycin 500 mg twice daily):

• Only use if local pneumococcal macrolide resistance is documented <25% 1, 2, 4
• Avoid in patients with any comorbidities, recent antibiotic use, or areas with ≥25% resistance due to risk of breakthrough bacteremia 1, 2

Adults With Comorbidities (Outpatient)

Combination therapy (preferred):

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days (strong recommendation, moderate quality evidence) 1, 2
• Alternative beta-lactams: cefpodoxime or cefuroxime can substitute if amoxicillin-clavulanate not tolerated 1

Fluoroquinolone monotherapy (alternative):

• Levofloxacin 750 mg orally once daily for 5 days (strong recommendation, moderate quality evidence) 1, 2, 5
• Moxifloxacin 400 mg orally once daily for 5 days 1, 2
• Fluoroquinolones are active against >98% of S. pneumoniae strains including penicillin-resistant isolates 1

Critical Decision Points and Pitfalls

When to avoid macrolide monotherapy:

• Any patient with comorbidities (diabetes, heart disease, COPD, renal/hepatic disease) 1, 2
• Areas where pneumococcal macrolide resistance ≥25% 1, 2
• Patients requiring hospitalization 1
• Recent antibiotic exposure within 90 days 1

When to choose a different antibiotic class:

• If patient received antibiotics within 90 days, select from a different class to reduce resistance risk 1

Fluoroquinolone cautions:

• Reserve for patients with comorbidities or when other options cannot be used 1
• Risk of tendinopathy, peripheral neuropathy, and CNS effects 1

Treatment Duration

Standard duration:

• 5-7 days for uncomplicated CAP once clinical stability achieved 1, 2
• Do not extend beyond 7 days in responding patients without specific indications 2

Extended duration (14-21 days) required only for:

• Suspected or confirmed Legionella pneumophila 1, 2
• Staphylococcus aureus infection 1, 2
• Gram-negative enteric bacilli 1, 2

Clinical Stability Criteria Before Discontinuation

Patient must achieve ALL of the following:

• Afebrile for 48-72 hours 2
• No more than one sign of clinical instability 2
• Resolution of vital sign abnormalities 1
• Ability to eat 1
• Normal mentation 1

Regional Variations to Consider

European and British guidelines favor:

• Amoxicillin as first-line therapy 1
• Erythromycin reserved for penicillin-allergic patients 1

US guidelines emphasize:

• Amoxicillin for healthy adults 1, 2
• Combination therapy or fluoroquinolones for those with comorbidities 1, 2

Cost and Efficacy Considerations

• Doxycycline demonstrates equivalent efficacy to levofloxacin in hospitalized patients at approximately half the cost ($64.98 vs $122.07 per treatment course) 3
• Azithromycin 1 g daily for 3 days shows non-inferior efficacy to amoxicillin-clavulanate 875/125 mg twice daily for 7 days (92.6% vs 93.1% clinical success) 6