Outpatient Treatment for Community-Acquired Pneumonia
For otherwise healthy adults without comorbidities, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line treatment for community-acquired pneumonia. 1
Treatment Algorithm Based on Patient Risk Factors
Healthy Adults WITHOUT Comorbidities
First-line options:
- Amoxicillin 1 g orally three times daily (strong recommendation, moderate quality evidence) 1
- Doxycycline 100 mg orally twice daily as an acceptable alternative (conditional recommendation, lower quality evidence) 1
- Macrolides (azithromycin 500 mg day 1, then 250 mg daily; OR clarithromycin 500 mg twice daily) ONLY if local pneumococcal macrolide resistance is documented <25% (conditional recommendation) 1
The recommendation for high-dose amoxicillin is based on studies demonstrating efficacy for inpatient CAP despite lack of atypical pathogen coverage, with a long safety track record. 1 Doxycycline provides broad-spectrum coverage including most common respiratory organisms but has limited clinical trial data. 1
Adults WITH Comorbidities
Comorbidities include: chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; asplenia; or recent antibiotic use within 90 days. 1
Two equally effective approaches:
Option 1 - Combination Therapy (strong recommendation):
- β-lactam: Amoxicillin-clavulanate 875 mg/125 mg twice daily OR 2,000 mg/125 mg twice daily; OR cefpodoxime 200 mg twice daily; OR cefuroxime 500 mg twice daily 1
- PLUS macrolide: Azithromycin 500 mg day 1, then 250 mg daily; OR clarithromycin 500 mg twice daily (strong recommendation for combination with macrolide) 1
- PLUS doxycycline 100 mg twice daily as alternative to macrolide (conditional recommendation, lower quality evidence) 1
Option 2 - Monotherapy (strong recommendation):
- Respiratory fluoroquinolone: Levofloxacin 750 mg daily; OR moxifloxacin 400 mg daily; OR gemifloxacin 320 mg daily 1
Duration of Therapy
Treat for a minimum of 5 days and until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability. 1 Typical duration for uncomplicated CAP is 5-7 days. 1
Critical Pitfalls to Avoid
Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and breakthrough pneumococcal bacteremia with resistant strains. 1, 2 Macrolide-resistant S. pneumoniae may also be resistant to doxycycline. 1
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and antimicrobial resistance concerns. 1 Reserve fluoroquinolones for patients with comorbidities or those who cannot tolerate first-line agents. 1
If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1
Broad-spectrum antibiotics (fluoroquinolones, β-lactams, β-lactam/macrolide combinations) are associated with increased risk of adverse drug events compared to narrow-spectrum regimens (macrolides, doxycycline), including nausea/vomiting, non-C. difficile diarrhea, and vulvovaginal candidiasis. 3
Evidence Quality and Rationale
Meta-analyses of 16 randomized controlled trials comparing antibiotic regimens for outpatient CAP revealed no differences in relevant outcomes between compared regimens, reflecting the paucity of high-quality data. 1 The committee considered RCTs from both outpatient and inpatient settings, antimicrobial resistance surveillance data, and antibiotic-related adverse events when formulating recommendations. 1
High-dose amoxicillin targets ≥93% of S. pneumoniae including drug-resistant strains and has demonstrated efficacy in multiple inpatient CAP studies. 1 The shift away from macrolide monotherapy as first-line therapy reflects rising pneumococcal resistance rates globally. 1, 2