Treatment for Outpatient Community-Acquired Pneumonia
For previously 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, 3
Treatment Algorithm Based on Patient Risk Stratification
Healthy Adults WITHOUT Comorbidities
First-line therapy:
- Amoxicillin 1 gram orally every 8 hours for 5-7 days (strong recommendation, moderate quality evidence) 1, 2, 3
Preferred alternative:
- Doxycycline 100 mg orally twice daily for 5-7 days (conditional recommendation, low quality evidence) 1, 2, 3
- Consider a 200 mg loading dose on day 1 to achieve adequate serum levels more rapidly 1, 3
- Provides broad-spectrum coverage including atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella) 1, 4
- Demonstrated comparable efficacy to fluoroquinolones in hospitalized patients at significantly lower cost 2, 4
Macrolide monotherapy (azithromycin or clarithromycin):
- Only use if local pneumococcal macrolide resistance is documented to be <25% (conditional recommendation, moderate quality evidence) 1, 2
- Breakthrough pneumococcal bacteremia occurs significantly more frequently with macrolide-resistant strains 2
Adults WITH Comorbidities
Comorbidities requiring combination therapy include: chronic heart disease, lung disease (COPD, asthma), liver disease, renal disease, diabetes mellitus, alcoholism, malignancies, asplenia, or immunosuppressing conditions/medications 1, 2, 5
First-line 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 total (strong recommendation, moderate quality evidence) 2, 3
- The beta-lactam targets S. pneumoniae and beta-lactamase-producing organisms 2
- The macrolide covers atypical pathogens (Mycoplasma, Chlamydophila, Legionella) 2, 5
- Combination beta-lactam/macrolide therapy achieves 91.5% favorable clinical outcomes 2
- Doxycycline 100 mg twice daily can substitute for azithromycin if macrolides are contraindicated 1, 2
Alternative beta-lactam options:
- Cefpodoxime or cefuroxime can replace amoxicillin-clavulanate if not tolerated 2
Fluoroquinolone monotherapy (alternative):
- Levofloxacin 750 mg orally once daily for 5 days (strong recommendation, moderate quality evidence) 1, 2, 3, 6
- Moxifloxacin 400 mg orally once daily for 5-7 days (strong recommendation, moderate quality evidence) 1, 2
- Active against >98% of S. pneumoniae strains, including penicillin-resistant isolates 2, 7
- Provides coverage of both typical and atypical organisms with convenient once-daily dosing 1, 7
Critical Decision Points to Prevent Treatment Failure
Recent Antibiotic Exposure
If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk (strong recommendation) 1, 2, 3
Regional Resistance Patterns
- Never use macrolide monotherapy in areas where pneumococcal macrolide resistance is ≥25% 1, 2, 3
- Never use macrolide monotherapy in patients with any comorbidities 2, 3
Fluoroquinolone Cautions
Reserve fluoroquinolones for patients with comorbidities or when other options cannot be used due to: 1, 2, 3
- Risk of tendinopathy and tendon rupture
- Peripheral neuropathy
- CNS effects (confusion, seizures)
- Cardiac arrhythmias (particularly in elderly patients or those with cardiac disease)
- Vascular disease complications
- Increased risk of Clostridium difficile infection
Avoid fluoroquinolones specifically in patients with: 2, 3
- History of cardiac arrhythmias
- Vascular disease
- History of C. difficile infection
Treatment Duration
Standard duration: 5-7 days for most uncomplicated cases 1, 2, 3
- Treat for a minimum of 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 2
Extended duration (14-21 days) required if: 2, 3
- Legionella pneumophila is suspected or confirmed
- Staphylococcus aureus is identified
- Gram-negative enteric bacilli are isolated
Special Populations and Considerations
Elderly Patients (≥65 years)
- Classify as having comorbidities and use combination therapy 2
- Amoxicillin-clavulanate 875 mg/125 mg twice daily PLUS azithromycin (no dose adjustment needed for mild renal impairment) 2
- Elderly patients are more susceptible to fluoroquinolone-associated torsades de pointes 8
Suspected Aspiration Pneumonia
- Amoxicillin-clavulanate or clindamycin to provide anaerobic coverage 2
Penicillin Allergy
Pregnancy
- Avoid doxycycline 3
- Avoid fluoroquinolones 8
- Use amoxicillin or amoxicillin-clavulanate with azithromycin if needed 8
Monitoring Response to Treatment
Clinical response should be assessed at day 2-3: 2, 3
- Fever should resolve within 2-3 days after initiating antibiotics 2, 3
- Assess for improved respiratory symptoms and hemodynamic stability 2
Patients should return if: 2
- Symptoms persist beyond 3 weeks
- Fever exceeds 4 days
- Dyspnea worsens
- Consciousness decreases
Do not automatically extend antibiotics beyond 5-7 days without documented indication 2, 3
Common Pitfalls to Avoid
Never use amoxicillin monotherapy for patients with comorbidities - insufficient coverage leads to treatment failure and resistance 2
Never use macrolide monotherapy as first-line in patients with comorbidities - significantly higher risk of breakthrough bacteremia 2, 3
Do not overuse fluoroquinolones in healthy patients without comorbidities - reserve for appropriate indications to minimize resistance and adverse events 1, 2, 3
Do not forget to assess for recent antibiotic exposure - using the same class increases resistance risk 1, 2, 3
Do not use cefuroxime for pneumococcal bacteremia when the organism is resistant in vitro - outcomes are worse than with other therapies 2