How to Choose Antibiotics in Community-Acquired Pneumonia
Initial Decision: Outpatient vs. Inpatient Treatment
The first critical decision is determining whether the patient requires hospitalization, which fundamentally changes antibiotic selection. Use validated severity scores (PSI or CURB-65) to stratify risk and guide this decision 1.
Outpatient Treatment (Non-Hospitalized Patients)
Healthy Adults Without Comorbidities
Amoxicillin 1 gram three times daily is the preferred first-line therapy for previously healthy adults without comorbidities 1, 2.
- Doxycycline 100 mg twice daily is an acceptable alternative if amoxicillin cannot be used 1, 2
- Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented to be <25% 1, 2, 3
- In areas with high macrolide resistance (>25%), macrolides should not be used as monotherapy due to treatment failure risk 1, 4
Adults With Comorbidities or Recent Antibiotic Use
For patients with comorbidities (diabetes, heart disease, lung disease, immunosuppression) or recent antibiotic exposure within 3 months, use combination therapy or respiratory fluoroquinolone monotherapy 1, 2.
Preferred regimens:
- Combination therapy: β-lactam (amoxicillin-clavulanate 2g twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) 1, 2
- Alternative: β-lactam PLUS doxycycline 100 mg twice daily 1
- Monotherapy option: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin) 1, 2, 5
Inpatient Treatment (Non-ICU)
For hospitalized patients not requiring ICU admission, use either β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy—both have strong evidence and equivalent efficacy 1, 2.
Preferred Regimens (Equal Strength of Recommendation)
Option 1 (Combination therapy):
- Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV/PO daily 1, 2, 6
- Alternative β-lactams: cefotaxime, ampicillin-sulbactam, or ceftaroline 1
Option 2 (Monotherapy):
Critical Considerations for Inpatient Treatment
- Administer the first antibiotic dose in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1, 3
- Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients 1, 2
- Avoid cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 1
- Switch from IV to oral therapy when patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function—typically by day 2-3 1, 2
ICU Treatment (Severe CAP)
All ICU patients require mandatory combination therapy with β-lactam PLUS either azithromycin OR respiratory fluoroquinolone 1, 2, 3.
Standard ICU Regimen
- Ceftriaxone 2 g IV daily OR cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours 1, 2
- PLUS azithromycin 500 mg IV daily 1, 2, 6
- OR PLUS levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2, 5
Special Situations Requiring Broader Coverage
Pseudomonas Risk Factors
Add antipseudomonal coverage if patient has: structural lung disease (bronchiectasis, COPD with frequent exacerbations), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa 1, 2, 3.
Antipseudomonal regimen:
- Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem, or meropenem) 1, 2
- PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 1, 5
- PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) for severe cases 1
MRSA Risk Factors
Add MRSA coverage if patient has: post-influenza pneumonia, cavitary infiltrates on imaging, prior MRSA infection/colonization, or recent hospitalization with IV antibiotics 1, 2, 3.
MRSA regimen additions:
- Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) 1, 2
- OR linezolid 600 mg IV every 12 hours 1, 2
Duration of Therapy
Treat for a minimum of 5 days and until patient is afebrile for 48-72 hours with no more than one sign of clinical instability 1, 2, 3.
- Standard duration: 5-7 days for uncomplicated CAP 1, 2
- Extended duration (14-21 days): Required for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2, 3
- Do not extend therapy beyond 7 days in responding patients without specific indications—this increases antimicrobial resistance risk 1
Penicillin-Allergic Patients
For documented penicillin or cephalosporin allergy, use respiratory fluoroquinolone monotherapy 1, 2.
- Outpatient: Levofloxacin 750 mg daily or moxifloxacin 400 mg daily 2, 5
- Inpatient non-ICU: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 1, 2, 5
- ICU: Respiratory fluoroquinolone PLUS aztreonam 2 g IV every 8 hours 1
Critical Pitfalls to Avoid
- Never use macrolide monotherapy in hospitalized patients—this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
- Avoid macrolide monotherapy in outpatients if local pneumococcal macrolide resistance exceeds 25% 1, 2, 3
- Do not delay antibiotic administration in hospitalized patients—give first dose in ED 1, 3
- Avoid automatically escalating to broad-spectrum antibiotics (antipseudomonal or anti-MRSA) without documented risk factors 1
- Reserve fluoroquinolones appropriately to prevent resistance—use β-lactam/macrolide combinations when possible 2, 7
- Obtain cultures before antibiotics in all hospitalized patients to allow targeted de-escalation 1, 2