What is the best antibiotic for treating pneumonia?

Best Antibiotic for Pneumonia

For outpatient community-acquired pneumonia in healthy adults without comorbidities, amoxicillin 1 gram three times daily for 5-7 days is the first-line treatment, with doxycycline 100 mg twice daily as the preferred alternative. 1, 2

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities (No Recent Antibiotics)

First-line choice:

• Amoxicillin 1 gram orally every 8 hours for 5-7 days 1, 2
• This targets Streptococcus pneumoniae, the most common pathogen (accounts for 48% of identified cases and two-thirds of bacteremic pneumonia) 1, 2

Alternative options:

• Doxycycline 100 mg orally twice daily for 5-7 days 1, 2
• Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for 4 days OR clarithromycin 500 mg twice daily) ONLY if local pneumococcal macrolide resistance is documented <25% 1, 3, 2

Critical caveat: Macrolide monotherapy should be avoided in most settings due to widespread resistance (>25% in many regions) and risk of breakthrough pneumococcal bacteremia with resistant strains 2

Adults With Comorbidities or Recent Antibiotic Use (Within 90 Days)

Combination therapy is mandatory:

• Amoxicillin-clavulanate 1-2 grams orally every 12 hours PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days 1, 2
• Alternative: Cefuroxime, cefpodoxime, or cefaclor PLUS macrolide 1

Fluoroquinolone monotherapy alternative:

• Levofloxacin 750 mg orally once daily for 5 days 1, 2
• Moxifloxacin 400 mg orally once daily for 5-7 days 1
• Warning: Reserve fluoroquinolones for patients who cannot use other options due to risks of tendinopathy, peripheral neuropathy, and CNS effects 2

Key principle: If antibiotics were used in the prior 90 days, select a different antibiotic class to reduce resistance risk 2

Hospitalized Non-ICU Patients

Preferred regimen:

• Ceftriaxone 1-2 grams IV once daily OR cefotaxime 1-2 grams IV every 8 hours PLUS azithromycin 500 mg IV/PO once daily OR clarithromycin 500 mg IV/PO twice daily 1, 2
• Alternative: Ampicillin-sulbactam 1.5-3 grams IV every 6 hours PLUS macrolide 1

Fluoroquinolone monotherapy alternative:

• Levofloxacin 750 mg IV once daily 1
• Moxifloxacin 400 mg IV once daily 1

Duration: 5-7 days for most cases 1, 2

Severe Pneumonia (ICU Patients)

Mandatory combination therapy:

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

Never use fluoroquinolone monotherapy in ICU patients 1

Extended duration: 10 days for severe pneumonia; extend to 14-21 days if Legionella, Staphylococcus aureus, or gram-negative enteric bacilli are suspected or confirmed 1, 2

Hospital-Acquired Pneumonia (HAP)

Low Risk (No MRSA Risk Factors, Not High Mortality Risk)

Monotherapy options:

• Piperacillin-tazobactam 4.5 grams IV every 6 hours 1
• Cefepime 2 grams IV every 8 hours 1
• Levofloxacin 750 mg IV daily 1
• Imipenem 500 mg IV every 6 hours OR meropenem 1 gram IV every 8 hours 1

High Risk (MRSA Risk Factors or High Mortality Risk)

Combination therapy required:

• Two antipseudomonal agents from different classes (avoid two β-lactams) PLUS MRSA coverage 1
• MRSA coverage: Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 1

MRSA risk factors include: IV antibiotics within 90 days, unit where >20% of S. aureus isolates are methicillin-resistant, or prior MRSA detection 1

Pediatric Pneumonia

Children Under 3 Years

First-line:

• Amoxicillin 80-100 mg/kg/day orally in 3 divided doses for 10 days 1
• Rationale: Pneumococcus is the predominant bacterial pathogen in this age group 1

If inadequate Hib vaccination (<3 doses) OR concurrent purulent otitis media:

• Amoxicillin-clavulanate 80 mg/kg/day (amoxicillin component) 1

Children Over 3 Years

If pneumococcal pneumonia suspected (lobar consolidation):

• Amoxicillin 80-100 mg/kg/day orally in 3 divided doses for 10 days 1

If atypical pneumonia suspected (Mycoplasma or Chlamydophila):

• Azithromycin 10 mg/kg day 1, then 5 mg/kg days 2-5 1
• Alternative: Clarithromycin 15 mg/kg/day divided twice daily for 14 days 1

Critical Treatment Principles

Assessment of clinical response:

• Evaluate at 48-72 hours (hospitalized) or 5-7 days (outpatients) 2
• Fever should resolve within 2-4 days; pneumococcal pneumonia often responds within 24 hours 1, 2
• Chest radiograph changes lag behind clinical improvement; do not repeat imaging in responding patients 1

Failure to respond indicates:

• Incorrect diagnosis, host failure, inappropriate antibiotic selection, resistant pathogen, adverse drug reaction, or complication (empyema, abscess) 1
• For non-severe pneumonia on amoxicillin monotherapy: add or substitute macrolide 1
• For non-severe pneumonia on combination therapy: switch to respiratory fluoroquinolone 1
• For severe pneumonia not responding: consider adding rifampicin 1

Switch from IV to oral therapy when:

• Clinical improvement evident 1
• Hemodynamically stable 1
• Able to ingest medications 1
• Typically occurs within 3-5 days 1

Common pitfalls to avoid:

• Using macrolide monotherapy in areas with >25% pneumococcal macrolide resistance 2
• Using macrolide monotherapy in patients with any comorbidities 2
• Using fluoroquinolone monotherapy in ICU patients 1
• Failing to cover MRSA in high-risk HAP patients 1
• Using azithromycin or other macrolides in patients who received them within 90 days 2