What is the initial treatment for pneumonia?

Initial Treatment for Pneumonia

For outpatients without comorbidities, start with amoxicillin 1g every 8 hours; for hospitalized non-ICU patients, use a β-lactam (ceftriaxone 1-2g IV daily) plus a macrolide (azithromycin 500mg IV daily); for severe ICU pneumonia, use an antipseudomonal β-lactam plus either a respiratory fluoroquinolone or a macrolide plus aminoglycoside. 1, 2, 3

Treatment Algorithm by Clinical Setting

Outpatient Treatment (Non-Hospitalized)

Previously healthy adults without comorbidities:

• First-line: Amoxicillin 1g every 8 hours orally 1, 2
• Alternative: Doxycycline 100mg twice daily (first dose 200mg) 2
• For atypical pathogen coverage: Macrolide monotherapy (azithromycin 500mg Day 1, then 250mg Days 2-5) is appropriate for patients under 40 years old 2

Outpatients with comorbidities or recent antibiotic use:

• Preferred: Respiratory fluoroquinolone (levofloxacin 750mg daily or moxifloxacin 400mg daily) 1, 2
• Alternative: β-lactam (amoxicillin 3g/day) plus macrolide 1, 2
• Patients with recent exposure to one antibiotic class should receive a different class due to resistance risk 2

Hospitalized Non-ICU Patients (Moderate-Risk)

Standard regimen options:

• Preferred: β-lactam (ceftriaxone 1-2g IV daily OR cefotaxime 1-2g IV every 8 hours) PLUS macrolide (azithromycin 500mg IV daily) 1, 3, 4
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750mg IV daily OR moxifloxacin 400mg IV daily) 1, 2, 3
• Most patients can be adequately treated with oral antibiotics if clinically appropriate 5

Critical timing consideration:

• Antibiotics must be administered in the Emergency Department within 4 hours of presentation 3
• Delays beyond 8 hours increase 30-day mortality by 20-30% 3

Severe CAP/ICU Patients

Without Pseudomonas risk factors:

• Non-antipseudomonal cephalosporin (ceftriaxone or cefotaxime) PLUS macrolide (azithromycin or clarithromycin) 1, 2
• Alternative: Respiratory fluoroquinolone (levofloxacin or moxifloxacin) with or without β-lactam 1, 2

With Pseudomonas risk factors (structural lung disease, recent hospitalization, recent broad-spectrum antibiotics):

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin OR levofloxacin 1, 2
• Alternative: Antipseudomonal β-lactam PLUS macrolide PLUS aminoglycoside (gentamicin, tobramycin, or amikacin) 1, 2

MRSA coverage:

• Add vancomycin or linezolid when community-acquired MRSA is suspected (prior MRSA infection, recent hospitalization, recent antibiotic use) 2

Duration and Transition of Therapy

Treatment duration:

• Minimum: 5 days with patient afebrile for 48-72 hours and clinically stable 1, 2, 3
• Standard: Generally should not exceed 8 days in responding patients 1, 2
• Extended (14-21 days): For Legionella, staphylococcal, or Gram-negative enteric bacilli pneumonia 5, 2

Switch to oral therapy:

• Transition when patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function 5, 2
• Up to half of hospitalized patients are eligible for oral switch by Day 3 5
• Sequential therapy (same drug IV to oral) includes doxycycline, linezolid, and fluoroquinolones 5
• Step-down therapy (different oral agent) with β-lactams and macrolides is clinically effective 5

Critical Pitfalls to Avoid

Fluoroquinolone misuse:

• Ciprofloxacin alone is inadequate for pneumococcal coverage—only levofloxacin 750mg and moxifloxacin have sufficient activity 3
• Reserve fluoroquinolones for β-lactam allergies or specific indications to prevent resistance 2
• FDA warnings exist regarding adverse events including QT prolongation, tendon rupture, and peripheral neuropathy 6

Macrolide resistance:

• S. pneumoniae resistance to macrolides ranges 30-40% and often co-exists with β-lactam resistance 2
• Macrolide monotherapy should not be used for hospitalized moderate-risk patients 3
• Combination therapy is preferred when regional resistance is high 3

Inadequate atypical coverage:

• Ensure coverage for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila 2
• While no mortality benefit exists for empirical atypical coverage, clinical success is significantly higher for Legionella when appropriate antibiotics are used 2

Failure to improve:

• Conduct careful review by experienced clinician if no improvement by Day 3 5
• Do not change antibiotics within first 72 hours unless marked clinical deterioration or bacteriologic data necessitate change 5
• Consider repeat chest radiograph, CRP, white cell count, and further microbiological testing 5, 2

Special Pathogen Considerations

Once etiology identified:

• Direct therapy at specific pathogen 1, 2
• For Legionella: levofloxacin, moxifloxacin, or azithromycin with or without rifampin 1
• For uncomplicated S. pneumoniae: 7-10 days typically sufficient 2

Viral testing:

• Test all patients for COVID-19 and influenza when community prevalence is high, as diagnosis affects treatment and infection prevention 4