What is the initial treatment for community-acquired pneumonia?

Initial Treatment for Community-Acquired Pneumonia

For outpatient adults without comorbidities, start amoxicillin 1 gram three times daily; for hospitalized non-ICU patients, use ceftriaxone 1-2 grams IV daily plus azithromycin 500 mg daily; for ICU patients, use ceftriaxone 2 grams IV daily plus azithromycin 500 mg daily or a respiratory fluoroquinolone. 1

Outpatient Treatment Algorithm

Healthy adults without comorbidities:

• Amoxicillin 1 gram orally three times daily is the preferred first-line therapy due to effectiveness against common CAP pathogens with moderate quality evidence 1
• Doxycycline 100 mg twice daily serves as an acceptable alternative (conditional recommendation) 1
• Macrolides (azithromycin 500 mg on day 1, then 250 mg daily, or clarithromycin 500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is <25% 1, 2

Adults with comorbidities (diabetes, heart disease, COPD, chronic kidney disease):

• Combination therapy with β-lactam (amoxicillin/clavulanate, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline 1
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin) 1, 3

Hospitalized Non-ICU Patients

Two equally effective first-line regimens with strong recommendation and high-quality evidence:

1. β-lactam plus macrolide combination:

   • Ceftriaxone 1-2 grams IV daily OR cefotaxime 1-2 grams IV every 8 hours OR ampicillin-sulbactam 3 grams IV every 6 hours 1
   • PLUS azithromycin 500 mg IV/PO daily OR clarithromycin 500 mg twice daily 1, 4, 5

2. Respiratory fluoroquinolone monotherapy:

   • Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 3

Critical timing consideration: Administer the first antibiotic dose while still in the emergency department, as delayed administration increases 30-day mortality by 20-30% 1

ICU-Level Severe CAP

Mandatory combination therapy for all ICU patients:

• β-lactam (ceftriaxone 2 grams IV daily, cefotaxime 1-2 grams IV every 8 hours, or ampicillin-sulbactam 3 grams IV every 6 hours) 1
• PLUS either azithromycin 500 mg IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2

Add coverage for resistant pathogens when specific risk factors present:

• For Pseudomonas aeruginosa risk factors (structural lung disease, recent hospitalization with IV antibiotics, prior P. aeruginosa isolation):

  • Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) 1
  • PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 1
  • PLUS aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily) 1

• For MRSA risk factors (prior MRSA infection, recent hospitalization with IV antibiotics, cavitary infiltrates, concurrent influenza):

  • Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 1, 2

Duration of Therapy

Standard duration: 5-7 days for uncomplicated CAP once clinical stability achieved 1, 5

Clinical stability criteria (all must be met):

• Afebrile for 48-72 hours 1
• Hemodynamically stable 1
• Clinically improving 1
• Able to take oral medications 1
• No more than one CAP-associated sign of clinical instability 1

Extended duration (14-21 days) required for:

• Legionella pneumophila 1
• Staphylococcus aureus 1
• Gram-negative enteric bacilli 1

Transition to Oral Therapy

Switch from IV to oral when patient meets all criteria:

• Hemodynamically stable 1
• Clinically improving 1
• Able to ingest medications 1
• Normal gastrointestinal function 1

Typical transition occurs by day 2-3 of hospitalization 1

Special Populations

Penicillin-allergic patients:

• Outpatient: Respiratory fluoroquinolone OR doxycycline 1
• Inpatient non-ICU: Respiratory fluoroquinolone monotherapy 1
• ICU: Respiratory fluoroquinolone plus aztreonam 2 grams IV every 8 hours 1

Elderly patients (≥65 years):

• Follow same algorithm as adults but consider higher doses of amoxicillin 6
• For hospitalized elderly: Combination oral therapy with amoxicillin plus macrolide (erythromycin or clarithromycin) 6
• When oral contraindicated: IV ampicillin or benzylpenicillin plus erythromycin or clarithromycin 6

Critical Pitfalls to Avoid

Avoid macrolide monotherapy in areas with high resistance: In regions where pneumococcal macrolide resistance exceeds 25%, macrolide monotherapy leads to treatment failure 1, 2

Avoid delayed antibiotic administration: Each hour of delay in hospitalized patients increases mortality risk 1, 2

Avoid inappropriate broad-spectrum antibiotics: Do not escalate to antipseudomonal or anti-MRSA coverage without documented risk factors, as this increases resistance and adverse effects 1

Avoid prolonged therapy without indication: Do not extend treatment beyond 7 days in responding patients without specific pathogens requiring longer courses, as this increases resistance risk 1

Obtain cultures before antibiotics: Blood and sputum cultures should be obtained in all hospitalized patients before initiating therapy to allow pathogen-directed de-escalation 1, 7

Consider recent antibiotic exposure: Patients who recently received β-lactam or macrolide therapy should receive antibiotics from a different class due to increased resistance risk 2