Outpatient Pneumonia Treatment
Healthy Adults Without Comorbidities
Amoxicillin 1 gram orally three times daily for 5-7 days is the first-line treatment for previously healthy outpatients with community-acquired pneumonia. 1, 2
- This regimen provides excellent coverage against Streptococcus pneumoniae, which accounts for 48% of identified CAP cases, with activity against 90-95% of pneumococcal strains including many with intermediate penicillin resistance 1
- Doxycycline 100 mg orally twice daily for 5-7 days serves as the preferred alternative for patients who cannot tolerate amoxicillin or have penicillin allergy 1, 2, 3
- Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for days 2-5, or clarithromycin 500 mg twice daily) should only be used when local pneumococcal macrolide resistance is documented to be <25% 1, 2, 3
Critical Pitfall 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
Adults With Comorbidities
Combination therapy with amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg on day 1, then 250 mg daily for 5-7 days total is the recommended first-line regimen for outpatients with comorbidities. 1, 2, 3
Comorbidities requiring combination therapy include: 1, 2
- Chronic heart, lung, liver, or renal disease
- Diabetes mellitus
- Alcoholism
- Malignancies
- Asplenia
- Immunosuppressing conditions or medications
- Recent antibiotic use within 90 days
Alternative Regimen
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg orally once daily OR moxifloxacin 400 mg orally once daily) for 5 days is equally effective but should be reserved for patients with contraindications to beta-lactams or macrolides due to FDA warnings about serious adverse events including tendinopathy, peripheral neuropathy, and CNS effects 1, 2, 4
Critical Decision Point
If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 2
Treatment Duration
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, 2, 3
- The typical duration for uncomplicated CAP is 5-7 days 1, 2
- Extend treatment to 14-21 days ONLY if Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli are identified 1, 2, 3
Special Populations
Suspected Aspiration Pneumonia
Use amoxicillin-clavulanate 875 mg/125 mg twice daily (or 2000 mg/125 mg twice daily for enhanced coverage) PLUS azithromycin to provide anaerobic coverage 1
Penicillin-Allergic Patients
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily OR moxifloxacin 400 mg daily) is the preferred alternative for patients with documented penicillin allergy 1, 2
Recent Antibiotic Exposure
Choose a different antibiotic class than recently used within 90 days to minimize resistance development 1, 2
Common Pitfalls to Avoid
Never use amoxicillin monotherapy in patients with comorbidities—this provides inadequate coverage for atypical pathogens and increases treatment failure risk 1, 2
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to resistance concerns and serious adverse events (tendinopathy, peripheral neuropathy, CNS effects, aortic dissection) 1, 2
Do not use macrolide monotherapy in patients with any comorbidities or in areas with ≥25% pneumococcal macrolide resistance—breakthrough bacteremia occurs significantly more frequently with resistant strains 1, 2
Avoid extending therapy beyond 7 days in responding patients without specific indications (Legionella, S. aureus, Gram-negative bacilli), as this increases antimicrobial resistance risk without improving outcomes 1, 2
Clinical Monitoring
Assess clinical response at day 2-3 for hospitalized patients or day 5-7 for outpatients. 1