What empiric antibiotic (abx) regimen should be started for a patient hospitalized with Community-Acquired Pneumonia (CAP)?

Empiric Antibiotic Treatment for Hospitalized Community-Acquired Pneumonia

For a patient hospitalized with community-acquired pneumonia (CAP), start combination therapy with a β-lactam plus a macrolide: specifically ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily. 1

Standard Regimen for Non-ICU Hospitalized Patients

The preferred empiric regimen is ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily, providing coverage for both typical bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1 This combination carries a strong recommendation with high-quality evidence from the Infectious Diseases Society of America and American Thoracic Society. 1

Alternative β-lactams include:

• Cefotaxime 1-2 g IV every 8 hours plus azithromycin 1
• Ampicillin-sulbactam 3 g IV every 6 hours plus azithromycin 1

Alternative Regimen: Respiratory Fluoroquinolone Monotherapy

Respiratory fluoroquinolone monotherapy is equally effective as β-lactam/macrolide combination therapy for hospitalized non-ICU patients. 1 Options include:

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

This regimen is particularly appropriate for penicillin-allergic patients. 1

When to Escalate to ICU-Level Therapy

If the patient requires ICU admission (septic shock, need for mechanical ventilation, or severe respiratory failure), escalate to:

• Ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily, OR 1
• Ceftriaxone 2 g IV daily plus levofloxacin 750 mg IV daily 1

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 1

Special Considerations: When to Add Broader Coverage

Add Antipseudomonal Coverage If:

• Structural lung disease (bronchiectasis, cystic fibrosis) 1
• Recent hospitalization with IV antibiotics within 90 days 1
• Prior respiratory isolation of Pseudomonas aeruginosa 1

Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV q6h, cefepime 2 g IV q8h, imipenem 500 mg IV q6h, or meropenem 1 g IV q8h) plus ciprofloxacin 400 mg IV q8h OR levofloxacin 750 mg IV daily, plus aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily). 1

Add MRSA Coverage If:

• Prior MRSA infection or colonization 1
• Recent hospitalization with IV antibiotics within 90 days 1
• Post-influenza pneumonia 1
• Cavitary infiltrates on imaging 1
• Local MRSA prevalence >20% among S. aureus isolates 1

Add: Vancomycin 15 mg/kg IV q8-12h (target trough 15-20 mg/mL) OR linezolid 600 mg IV q12h. 1

Critical Timing Considerations

Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department. 1 Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients. 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 Typical duration for uncomplicated CAP is 5-7 days. 1

Extend duration to 14-21 days if Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli are identified. 1

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient is:

• Hemodynamically stable 1
• Clinically improving 1
• Able to take oral medications 1
• Has normal GI function 1

This typically occurs by day 2-3 of hospitalization. 1

Oral step-down options:

• Amoxicillin 1 g orally three times daily plus azithromycin 500 mg orally daily 1
• Continue levofloxacin 750 mg orally daily (if started on fluoroquinolone) 1

Common Pitfalls to Avoid

Never use macrolide monotherapy in hospitalized patients, as it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae. 1 Macrolide monotherapy should only be considered for carefully selected outpatients in areas where pneumococcal macrolide resistance is documented <25%. 1

Avoid indiscriminate use of broad-spectrum antibiotics (antipseudomonal agents, carbapenems, MRSA coverage) unless specific risk factors are present, as this increases resistance, toxicity, and Clostridioides difficile infection risk. 1

Do not use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy for standard CAP without risk factors for resistant organisms. 1 These agents should be reserved for patients with documented risk factors for Pseudomonas or other resistant pathogens. 1

Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 1