What is the first line of antibiotic therapy for pneumonia?

First-Line Antibiotic Therapy for Pneumonia

For community-acquired pneumonia (CAP), amoxicillin is the first-line antibiotic for outpatient treatment in otherwise healthy adults, while hospitalized patients with non-severe CAP should receive combination therapy with amoxicillin plus a macrolide (erythromycin or clarithromycin). 1

Outpatient Management (Community-Acquired Pneumonia)

Healthy adults without comorbidities:

• Amoxicillin 1g three times daily is the preferred first-line agent 1
• Doxycycline 100mg twice daily serves as an alternative for penicillin-allergic patients 1

Adults with comorbidities:

• Combination therapy is required: amoxicillin/clavulanate or a cephalosporin PLUS either a macrolide or doxycycline 1
• This broader coverage accounts for increased risk of resistant organisms and atypical pathogens 1

Hospitalized Patients (Non-Severe CAP)

Most hospitalized patients can be treated with oral antibiotics:

• Combined oral therapy with amoxicillin PLUS a macrolide (erythromycin or clarithromycin) is the preferred regimen 2, 1
• This combination provides coverage for both typical bacterial pathogens (particularly Streptococcus pneumoniae) and atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella) 2

When oral therapy is contraindicated:

• Intravenous ampicillin or benzylpenicillin PLUS intravenous erythromycin or clarithromycin 2
• Recent evidence suggests ampicillin may be comparable to ceftriaxone with lower rates of Clostridioides difficile infection 3

Monotherapy considerations (limited circumstances):

• Amoxicillin alone may be appropriate for patients previously untreated in the community or those admitted for non-clinical reasons (elderly, socially isolated) 2
• Macrolide monotherapy may be suitable for patients who failed adequate amoxicillin therapy prior to admission, though combination therapy remains preferred 2

Hospitalized Patients (Severe CAP)

Severe pneumonia requires immediate parenteral antibiotics:

• Intravenous β-lactamase stable antibiotic (co-amoxiclav, cefuroxime, cefotaxime, or ceftriaxone) PLUS intravenous macrolide (clarithromycin or erythromycin) 2, 1
• This combination has been associated with relative mortality reductions of 26% to 68% compared to β-lactam monotherapy in observational studies 4

Alternative for β-lactam or macrolide intolerance:

• Fluoroquinolone with enhanced pneumococcal activity (levofloxacin) PLUS intravenous benzylpenicillin 2
• Fluoroquinolone monotherapy has shown relative mortality reductions of 30% to 43% compared to β-lactam monotherapy 4
• However, fluoroquinolones should not be first-line due to resistance concerns and limited experience 2

Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

Patients NOT at high mortality risk and no MRSA risk factors:

• Single agent: piperacillin-tazobactam 4.5g IV q6h, cefepime 2g IV q8h, levofloxacin 750mg IV daily, imipenem 500mg IV q6h, or meropenem 1g IV q8h 2

Patients at high mortality risk OR recent IV antibiotic use (within 90 days):

• Two antipseudomonal agents from different classes (avoid two β-lactams) 2
• PLUS vancomycin 15mg/kg IV q8-12h (target trough 15-20 mg/mL) OR linezolid 600mg IV q12h for MRSA coverage 2
• High mortality risk includes need for ventilatory support or septic shock 2

Key VAP considerations:

• Antibiotic choice should be based on prior antibiotic exposure—patients without previous antibiotics more commonly have Gram-positive cocci and Haemophilus influenzae, while prior antibiotic use predicts non-fermentative Gram-negative bacilli 2
• Patients with COPD or >7 days of mechanical ventilation require combination therapy with antipseudomonal activity due to increased Pseudomonas aeruginosa risk 2
• MRSA is not expected without prior antibiotic administration; vancomycin should not be empiric in antibiotic-naive patients 2
• Notably, vancomycin for MRSA VAP is associated with very poor outcomes (≈50% mortality), suggesting β-lactams are superior for methicillin-sensitive S. aureus 2

Pediatric Pneumonia

Children under 5 years:

• Amoxicillin is first-line for mild to moderate disease 2, 1, 5
• Alternatives include co-amoxiclav, cefaclor, erythromycin, clarithromycin, or azithromycin 2
• Young children with mild symptoms may not require antibiotics at all 2

Children 5 years and older:

• Macrolide antibiotics may be first-line due to higher prevalence of Mycoplasma pneumoniae 2
• Amoxicillin remains appropriate if S. pneumoniae is suspected 2

Severe pediatric pneumonia:

• Intravenous co-amoxiclav, cefuroxime, or cefotaxime 2
• If S. pneumoniae confirmed, amoxicillin, ampicillin, or penicillin alone is sufficient 2

Duration of Therapy

Standard duration:

• 7 days for most uncomplicated CAP 1
• 10 days for severe microbiologically undefined pneumonia 2, 1
• 14-21 days for Legionella, staphylococcal, or Gram-negative enteric bacilli pneumonia 2, 1

Pediatric duration:

• 3-5 days of oral amoxicillin for ambulatory treatment 5

Timing and Transition Considerations

Time to first antibiotic dose:

• Initiation within 4-8 hours of hospital arrival is associated with relative mortality reductions of 5% to 43% in large observational studies 4
• Severe pneumonia requires immediate parenteral antibiotics upon diagnosis 2

IV to oral transition:

• Use objective clinical criteria (clinical stability, improved oxygenation, ability to take oral medications) rather than arbitrary time points 4
• This approach reduces hospital length of stay by approximately 1.9 days without increasing treatment failure 4

Common Pitfalls and Caveats

Avoid these errors:

• Do not use vancomycin empirically for HAP/VAP in patients without prior antibiotic exposure—MRSA is unlikely and outcomes are poor even when present 2
• Do not add antifungal therapy for Candida colonization in respiratory samples; treat only with sterile site isolation or histologic evidence 2
• Do not use fluoroquinolones as first-line for CAP due to resistance concerns, though they remain valuable alternatives 2
• Do not assume β-lactam monotherapy is adequate for hospitalized CAP patients—combination with a macrolide improves mortality 4
• Prolonging antibiotic treatment does not prevent VAP recurrences, which typically represent relapse rather than reinfection 2

Modification based on response:

• If patients on amoxicillin monotherapy fail to improve within 48 hours, add or substitute a macrolide to cover atypical pathogens 2
• For hospitalized patients on combination therapy not improving, consider switching to a fluoroquinolone with pneumococcal coverage 2
• Rifampicin addition may be considered for severe pneumonia unresponsive to combination therapy 2