What are the initial treatment recommendations for Community-Acquired Pneumonia (CAP)?

Community-Acquired Pneumonia Treatment Recommendations

For outpatient CAP without comorbidities, start with amoxicillin 1 g three times daily; for hospitalized non-ICU patients, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily; and for ICU patients, use β-lactam plus either azithromycin or a respiratory fluoroquinolone. 1, 2

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g three times daily is the preferred first-line therapy for healthy outpatients without comorbidities, based on strong recommendation and moderate quality evidence 2
• Doxycycline 100 mg twice daily (with first dose of 200 mg to achieve rapid serum levels) serves as an acceptable alternative 1, 2
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is <25%, as resistance rates of 30-40% are common in many regions 1, 2

Outpatients With Comorbidities or Recent Antibiotic Use

• Combination therapy with β-lactam (amoxicillin-clavulanate, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline is recommended 1, 2
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) is an equally effective alternative 1, 2
• Patients with recent exposure to one antibiotic class should receive treatment from a different class due to increased resistance risk 1

Hospitalized Non-ICU Patients

The standard regimen is ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily, with strong recommendation and high-quality evidence 1, 2, 3

Alternative options include:

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2
• β-lactam plus doxycycline (conditional recommendation, lower quality evidence) 2

The first antibiotic dose must be administered while still in the emergency department, as delayed administration is associated with increased mortality 1, 2

Severe CAP/ICU Treatment

Mandatory combination therapy with 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 daily or respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2

Risk Factors for Pseudomonas Requiring Broader Coverage

When structural lung disease, recent hospitalization with IV antibiotics, or prior Pseudomonas aeruginosa isolation is present:

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus ciprofloxacin 400 mg IV every 8 hours or levofloxacin 750 mg IV daily 1, 2
• Alternative: aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily) plus azithromycin or antipneumococcal fluoroquinolone 1, 2

Risk Factors for MRSA Requiring Additional Coverage

When post-influenza pneumonia, cavitary infiltrates, prior MRSA infection, recent hospitalization, or recent antibiotic use is present:

• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) or linezolid 600 mg IV every 12 hours 1, 2

Duration of Therapy

• Minimum of 5 days for uncomplicated CAP, with patient required to be afebrile for 48-72 hours and have no more than one sign of clinical instability before discontinuing 1, 2
• Standard duration is 5-7 days for most patients 2
• Extend to 14-21 days for Legionella, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2
• Treatment should generally not exceed 8 days in a responding patient 1

Transition to Oral Therapy

Switch from IV to oral therapy when patients are hemodynamically stable, clinically improving, able to take oral medications, and have normal GI function, typically by day 2-3 of hospitalization 2

Critical Pitfalls to Avoid

• Reserve fluoroquinolones for patients with β-lactam allergies or specific indications to prevent resistance development, despite FDA approval for CAP 1, 4
• Avoid macrolide monotherapy in areas with high (>25%) pneumococcal macrolide resistance or in patients with recent hospitalization, chronic diseases, or prior antibiotic exposure 1, 2
• Do not use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 2
• Ensure adequate coverage for atypical pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila), as clinical success is significantly higher when atypical antibiotics are used for Legionella 1, 5
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation 2
• Do not delay antibiotic administration beyond arrival in the emergency department for hospitalized patients, as this increases 30-day mortality by 20-30% 2

Special Considerations for Penicillin-Allergic Patients

• Respiratory fluoroquinolone (levofloxacin or moxifloxacin) is the preferred option for penicillin-allergic patients requiring hospitalization 2
• For ICU patients with penicillin allergy: respiratory fluoroquinolone plus aztreonam 2 g IV every 8 hours 2