Recommended Antibiotics for Community-Acquired Respiratory Infections in Adults
For previously healthy adults without comorbidities, amoxicillin 1 gram three times daily for 5-7 days is the first-line antibiotic, with doxycycline 100 mg twice daily as the preferred alternative. 1
Outpatient Treatment Algorithm
Healthy Adults Without Comorbidities
First-line therapy:
- Amoxicillin 1 gram orally three times daily for 5-7 days (strong recommendation, moderate quality evidence) 1
- This provides activity against 90-95% of Streptococcus pneumoniae strains, the most common pathogen accounting for 48% of identified cases 1
Alternative options:
- Doxycycline 100 mg orally twice daily for 5-7 days (conditional recommendation, low quality evidence) 1
- Macrolide monotherapy (azithromycin or clarithromycin) ONLY if local pneumococcal macrolide resistance is documented to be <25% 1
Critical caveat: Macrolide monotherapy should be avoided in areas with ≥25% pneumococcal macrolide resistance due to significantly increased risk of breakthrough pneumococcal bacteremia with resistant strains 1
Adults With Comorbidities
Comorbidities requiring enhanced therapy include: chronic heart disease, lung disease (including COPD), liver disease, renal disease, diabetes mellitus, alcoholism, malignancies, asplenia, or immunosuppression 1
First-line combination therapy:
- Amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days total (strong recommendation, moderate quality evidence) 1, 2
- Alternative beta-lactam: Amoxicillin-clavulanate 500/125 mg three times daily PLUS macrolide 1, 2
Alternative monotherapy:
- Levofloxacin 750 mg orally once daily for 5 days (strong recommendation, moderate quality evidence) 1, 3
- Moxifloxacin 400 mg orally once daily for 5 days 1
Rationale for combination therapy: The beta-lactam component targets S. pneumoniae while the macrolide covers atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila), achieving 91.5% favorable clinical outcomes 1
Inpatient Non-ICU Treatment
Standard regimen:
- Ceftriaxone 1-2 grams IV once daily PLUS azithromycin 500 mg IV or oral daily (strong recommendation, moderate quality evidence) 1
- Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) 1
Duration: Minimum 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 1
Severe CAP (ICU Patients)
Standard regimen:
- Ceftriaxone 2 grams IV once daily PLUS azithromycin 500 mg IV daily 1
- Alternative: Beta-lactam PLUS respiratory fluoroquinolone 1
When Pseudomonas aeruginosa is suspected (structural lung disease, recent hospitalization with IV antibiotics within 90 days):
- Antipseudomonal beta-lactam (cefepime 2 grams IV every 8 hours) PLUS ciprofloxacin or aminoglycoside PLUS macrolide 1
Critical Treatment Considerations
Recent antibiotic exposure (within 90 days):
- Select an agent from a different antibiotic class to reduce resistance risk 1
Treatment duration:
- Standard: 5-7 days for uncomplicated pneumonia 1
- Extended (14-21 days) ONLY for: Legionella pneumophila, Staphylococcus aureus, or gram-negative enteric bacilli 1
Fluoroquinolone cautions:
- Reserve for patients with comorbidities or when other options cannot be used due to risk of tendinopathy, peripheral neuropathy, and CNS effects 1
- Fluoroquinolones are active against >98% of S. pneumoniae strains, including penicillin-resistant isolates 1
Common Pitfalls to Avoid
Never use:
- Macrolide monotherapy in patients with any comorbidities 1
- Macrolide monotherapy in areas with ≥25% pneumococcal macrolide resistance 1
- Beta-lactam monotherapy for hospitalized patients—always add macrolide or fluoroquinolone 1
- Cephalosporin monotherapy for outpatients—lacks atypical coverage 1
Monitoring response: