What is the best treatment for bacterial pneumonia in adults?

Best Medicine for Bacterial Pneumonia in Adults

For hospitalized adults with non-severe community-acquired pneumonia, use combination therapy with a β-lactam (ceftriaxone 1-2g daily, cefotaxime 1-2g every 8 hours, or ampicillin-sulbactam 1.5-3g every 6 hours) plus a macrolide (azithromycin 500mg daily or clarithromycin 500mg twice daily), or alternatively, monotherapy with a respiratory fluoroquinolone (levofloxacin 750mg daily or moxifloxacin 400mg daily). 1

Treatment by Clinical Setting

Hospitalized Patients (Non-ICU, Non-Severe CAP)

First-line options (equally recommended):

• β-lactam + macrolide combination (strong recommendation, high-quality evidence) 1

  • Preferred β-lactams: ceftriaxone 1-2g daily, cefotaxime 1-2g every 8 hours, ampicillin-sulbactam 1.5-3g every 6 hours, or ceftaroline 600mg every 12 hours 1
  • Macrolides: azithromycin 500mg daily or clarithromycin 500mg twice daily 1

• Respiratory fluoroquinolone monotherapy (strong recommendation, high-quality evidence) 1

  • Levofloxacin 750mg daily or moxifloxacin 400mg daily 1

Alternative for patients with contraindications to both macrolides and fluoroquinolones:

• β-lactam + doxycycline 100mg twice daily (conditional recommendation, low-quality evidence) 1

Severe CAP Requiring ICU Admission

Mandatory combination therapy:

• β-lactam (ceftriaxone 2g daily, cefotaxime 1g every 8 hours, or ampicillin-sulbactam) PLUS either azithromycin or a respiratory fluoroquinolone (strong recommendation) 1
  • The macrolide-containing regimen shows an 18% relative risk reduction in mortality (3% absolute risk reduction) in critically ill patients based on meta-analysis of nearly 10,000 patients 1

For Pseudomonas aeruginosa risk factors:

• Use antipseudomonal β-lactam (piperacillin-tazobactam 4.5g every 6 hours, cefepime, imipenem, or meropenem) PLUS either ciprofloxacin or levofloxacin 750mg, OR the β-lactam plus an aminoglycoside and azithromycin 1

For suspected MRSA:

• Add vancomycin or linezolid to the above regimens 1

Evidence Quality and Nuances

The 2019 ATS/IDSA guidelines 1 represent the most current high-quality evidence and supersede the 2007 guidelines 1. Key findings include:

• Systematic review of 16 RCTs (4,809 patients) found fluoroquinolone monotherapy resulted in fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations, though mortality rates were similar 1

• Meta-analysis of observational studies showed both β-lactam/macrolide and fluoroquinolone monotherapy were superior to β-lactam monotherapy alone for mortality reduction 1

• For severe CAP specifically, macrolide-containing regimens demonstrated significant mortality benefit in critically ill patients 1

Treatment Duration

• Minimum 5 days for uncomplicated CAP, with patient afebrile for 48-72 hours and no more than one sign of clinical instability before discontinuation 1
• 7 days is appropriate for most non-severe cases 1, 2
• 10 days for severe, microbiologically undefined pneumonia 1, 2
• 14-21 days for Legionella, staphylococcal, or gram-negative enteric bacilli pneumonia 1, 2

Critical Clinical Pearls

Route of administration:

• Start IV antibiotics in the emergency department for admitted patients 1
• Switch to oral therapy when hemodynamically stable, clinically improving, able to ingest medications, and with functioning GI tract 1

Common pitfall - macrolide resistance:

• In regions with >25% high-level macrolide-resistant S. pneumoniae, avoid macrolide monotherapy and use combination therapy or fluoroquinolones 1

Fluoroquinolone considerations:

• Reserve for specific indications due to FDA safety warnings and resistance concerns 1
• Levofloxacin 750mg daily for 5 days is equally effective as 500mg for 7-10 days in CAP 3, 4, 5
• Previous fluoroquinolone exposure may preclude use due to resistance 3

Treatment failure approach:

• For non-severe CAP on amoxicillin monotherapy: add or substitute a macrolide 1
• For patients on combination therapy: switch to fluoroquinolone with pneumococcal coverage 1
• For severe CAP not responding: consider adding rifampicin 1