Oral Antibiotics for Community-Acquired Pneumonia
For outpatient community-acquired pneumonia, start amoxicillin 500-1000 mg every 8 hours PLUS a macrolide (azithromycin 500 mg day 1, then 250 mg daily for 4 days OR clarithromycin 500 mg twice daily), or alternatively use a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) as monotherapy. 1
Treatment Algorithm by Patient Risk Category
Outpatients Without Comorbidities
First-line options:
- Amoxicillin 1 g every 8 hours 1
- Doxycycline 100 mg twice daily (consider 200 mg first dose) 1
- Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for 4 days OR clarithromycin 250-500 mg twice daily for at least 5 days) 1
These regimens are appropriate for previously healthy patients with no risk factors for drug-resistant Streptococcus pneumoniae (DRSP) 1.
Outpatients With Comorbidities
Combination therapy is preferred:
- Amoxicillin-clavulanate 1 g every 8 hours PLUS a macrolide 1
- Cefuroxime axetil 750 mg twice daily PLUS a macrolide 1
Alternative monotherapy:
- Respiratory fluoroquinolone: levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily 1, 2
Comorbidities include chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; or asplenia 1.
Hospitalized Patients (Non-ICU)
For patients requiring hospitalization but not ICU admission:
- Oral erythromycin 1 g every 8 hours 1
- Oral azithromycin 500 mg daily for 3 days OR 500 mg day 1, then 250 mg daily for 5 days 1, 3
- Oral clarithromycin 250-500 mg twice daily for at least 5 days 1, 3
Most hospitalized patients can be adequately treated with oral antibiotics if they can tolerate oral intake 1. Combined oral therapy with amoxicillin and a macrolide is preferred for patients requiring hospital admission for clinical reasons 1.
Special Considerations
Penicillin Allergy
- Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) 1, 2
- Doxycycline 100 mg twice daily 1
Areas with High DRSP Prevalence
Macrolide monotherapy should be avoided in areas with high rates of resistant S. pneumoniae 1. However, clinical studies demonstrate that azithromycin achieves clinical success even against macrolide-resistant pneumococcal strains, suggesting an "in vivo-in vitro paradox" 4.
Suspected Atypical Pathogens
When Mycoplasma pneumoniae, Chlamydophila pneumoniae, or Legionella pneumophila are suspected:
- Macrolide therapy is essential (azithromycin or clarithromycin) 1, 5
- Respiratory fluoroquinolones also provide excellent atypical coverage 1
Treatment should last 21 days when Legionella infection is suspected or confirmed 1.
Duration of Therapy
- Minimum 5 days of treatment for uncomplicated CAP 1
- Patient must be afebrile for 48-72 hours before discontinuation 1
- At least 7 days for most regimens (except azithromycin and clarithromycin which have shorter courses) 1
- Azithromycin: 3-5 day courses are effective 3, 6, 7
Common Pitfalls to Avoid
Fluoroquinolone overuse: Reserve respiratory fluoroquinolones for patients with treatment failure, documented highly drug-resistant pneumococci (penicillin MIC ≥4 mcg/mL), or true penicillin/macrolide allergies to limit emergence of fluoroquinolone resistance 8.
Inadequate atypical coverage: Failure to include macrolide or fluoroquinolone therapy may result in treatment failure when atypical pathogens are present, which account for up to 29.5% of CAP cases 5.
Premature discontinuation: Ensure clinical stability criteria are met before stopping antibiotics, including resolution of fever and no more than one sign of clinical instability 1.
Geographic resistance patterns: In areas with high beta-lactamase-producing Haemophilus influenzae, amoxicillin-clavulanate is preferred over amoxicillin alone 1.