What is the first line treatment for an adult patient with community-acquired pneumonia (CAP)?

First-Line Treatment for Community-Acquired Pneumonia

For healthy outpatient adults without comorbidities, amoxicillin 1 g orally three times daily is the preferred first-line treatment, with doxycycline 100 mg twice daily as an acceptable alternative. 1, 2

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line agent based on moderate quality evidence supporting effectiveness against common CAP pathogens 1, 2
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries lower quality evidence 1, 2
• Macrolides should only be used when local pneumococcal macrolide resistance is documented <25% due to concerns about resistance development and treatment failure 1, 2

Outpatients With Comorbidities

Comorbidities include COPD, diabetes, chronic heart/liver/renal disease, malignancy, or recent antibiotic use within 3 months 1

Two equally effective options exist:

• Combination therapy: β-lactam (amoxicillin-clavulanate 875 mg/125 mg twice daily, cefpodoxime 200 mg twice daily, or cefuroxime 500 mg twice daily) PLUS macrolide (azithromycin 500 mg day 1, then 250 mg daily OR clarithromycin 500 mg twice daily) or doxycycline 100 mg twice daily 1, 2

• Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily 1, 2

Inpatient Treatment (Non-ICU)

For hospitalized patients not requiring ICU admission, two equally effective regimens exist with strong recommendations and high-quality evidence:

• β-lactam plus macrolide: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily 1, 3

  • Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours 1
  • This combination provides coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1

• Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 4

  • Systematic reviews demonstrate fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations 5

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease: 1, 2

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

Special Populations Requiring Broader Coverage

Pseudomonas Risk Factors

Add antipseudomonal coverage for patients with structural lung disease, recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa 1, 2

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

MRSA Risk Factors

Add MRSA coverage for patients with prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates 1, 2

• Add vancomycin 15 mg/kg IV every 8-12 hours OR linezolid 600 mg IV every 12 hours to the base regimen 1

Duration of Therapy

• Treat for a minimum of 5 days and until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability 1, 3
• Typical duration for uncomplicated CAP is 5-7 days 1, 3
• Extended duration (14-21 days) is required for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure 1, 2
• Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1, 3
• Avoid indiscriminate use of vancomycin or piperacillin-tazobactam without documented risk factors for MRSA or Pseudomonas, as this was associated with inappropriate prescribing in 13% and 8% of ward patients respectively 6
• Avoid fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns 1
• For penicillin-allergic patients, use respiratory fluoroquinolone as the preferred alternative rather than attempting cross-reactive cephalosporins 1, 2