Oral Antibiotics for Pneumonia in Stable Patients
For stable outpatients with community-acquired pneumonia, amoxicillin 1 gram three times daily for 5-7 days is the first-line oral antibiotic, with doxycycline 100 mg twice daily as an acceptable alternative for patients without comorbidities. 1
Treatment Algorithm Based on Patient Characteristics
Healthy Adults Without Comorbidities
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, the most common pathogen accounting for 48% of identified CAP cases 1
Alternative options:
- Doxycycline 100 mg orally twice daily for 5-7 days (conditional recommendation, low quality evidence) 1, 2
- Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5; or clarithromycin 500 mg twice daily) ONLY if local pneumococcal macrolide resistance is documented <25% 1, 2
Adults With Comorbidities
Comorbidities requiring combination therapy include: chronic heart/lung/liver/renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, or age >65 years 1, 2
Preferred combination therapy:
- Amoxicillin-clavulanate 875/125 mg twice daily (or 2000/125 mg twice daily for enhanced formulation) PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days total 1, 2
- Alternative β-lactams: cefpodoxime or cefuroxime 500 mg twice daily can substitute if amoxicillin-clavulanate is not tolerated 1
- Doxycycline 100 mg twice daily can substitute for the macrolide component 1
Alternative monotherapy:
- Respiratory fluoroquinolone: levofloxacin 750 mg once daily for 5 days OR moxifloxacin 400 mg once daily for 5 days (strong recommendation, moderate quality evidence) 1, 2
- However, fluoroquinolones should be reserved for specific situations due to FDA warnings about serious adverse events including tendinopathy, peripheral neuropathy, and CNS effects 2
Critical Decision Points to Prevent Treatment Failure
Never use macrolide monotherapy in the following situations:
- Patients with any comorbidities 1
- Areas where pneumococcal macrolide resistance ≥25% 1, 2
- Patients with recent antibiotic use within 90 days 1
- Patients requiring hospitalization 1
If recent antibiotic exposure (within 90 days): Select an agent from a different antibiotic class to reduce resistance risk 1, 2
Treatment Duration and Monitoring
Standard duration: 5-7 days for uncomplicated pneumonia once clinical stability is achieved 1, 2
Clinical stability criteria (must meet ALL):
- Afebrile for 48-72 hours 1
- No more than one sign of clinical instability 1
- Ability to eat and normal mentation 1
Extended duration (14-21 days) required for:
Follow-up assessment:
- Clinical review at 48 hours or sooner if clinically worsening 1
- Scheduled follow-up at 6 weeks for all patients, with chest radiograph reserved for persistent symptoms, physical signs, or high malignancy risk (smokers, age >50 years) 1
When Oral Therapy is Inappropriate
Patients requiring hospitalization and IV antibiotics include those with:
- Moderate to severe illness or hemodynamic instability 3
- Inability to tolerate oral medications 3
- Severe respiratory distress 4
- Known or suspected bacteremia 3
- Cystic fibrosis or nosocomial infection 3
- Significant underlying health problems compromising ability to respond (immunodeficiency, functional asplenia) 3
- Elderly or debilitated patients requiring hospitalization 3
Common Pitfalls to Avoid
Macrolide resistance: Breakthrough pneumococcal bacteremia occurs significantly more frequently with macrolide-resistant strains when macrolide monotherapy is used 1
Inadequate coverage: Amoxicillin monotherapy is insufficient for patients with comorbidities and leads to treatment failure 1
Fluoroquinolone overuse: Avoid indiscriminate use in uncomplicated outpatient CAP due to resistance concerns and serious adverse events 1
Delayed treatment: Antibiotic administration should not be delayed, as this increases mortality risk 4