What are the recommended empirical antibiotics for a patient with community-acquired pneumonia (CAP)?

Empirical Antibiotics for Community-Acquired Pneumonia

For outpatient CAP without comorbidities, use amoxicillin 1 g three times daily; for hospitalized non-ICU patients, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily; for ICU patients, use ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily. 1

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, providing excellent coverage against Streptococcus pneumoniae including most drug-resistant strains 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative if amoxicillin cannot be tolerated 1
• Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented <25%, as resistance rates now exceed this threshold in most regions 1, 2

Adults With Comorbidities (COPD, Diabetes, Heart/Liver/Renal Disease, Malignancy)

• Use combination therapy: amoxicillin-clavulanate 875/125 mg twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1
• Alternative: respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily OR moxifloxacin 400 mg daily) 1, 2
• If the patient received antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk 1

Hospitalized Non-ICU Patients

Standard Regimen

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (IV or oral) provides coverage for both typical bacterial pathogens and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 1
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) is equally effective as combination therapy 1, 3

Penicillin-Allergic Patients

• Respiratory fluoroquinolone (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) is the preferred alternative 1
• If fluoroquinolones are contraindicated: aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg daily 1

Transition to Oral Therapy

• Switch from IV to oral when the patient is hemodynamically stable, clinically improving, afebrile for 48-72 hours, able to take oral medications, and has normal GI function—typically by day 2-3 1
• Oral step-down: amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily 1

Severe CAP Requiring ICU Admission

Mandatory Combination Therapy

• Ceftriaxone 2 g IV daily (OR cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours) PLUS azithromycin 500 mg IV daily 1
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) 1
• Monotherapy is never adequate for ICU-level severity 1

Risk Factors for Pseudomonas aeruginosa

If the patient has structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa:

• Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem 500 mg IV every 6 hours, OR meropenem 1 g IV every 8 hours) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin OR tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 500 mg IV daily 4, 1

Risk Factors for MRSA

If the patient has prior MRSA infection/colonization, recent hospitalization with IV antibiotics within 90 days, post-influenza pneumonia, or cavitary infiltrates on imaging:

• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours to the base regimen 4, 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: 5-7 days total 1, 5
• Extend to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1

Critical Timing and Diagnostic Considerations

Antibiotic Administration

• Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1

Diagnostic Testing for Hospitalized Patients

• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients 1
• Consider urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1

Common Pitfalls to Avoid

• Never use macrolide monotherapy (azithromycin, clarithromycin) for hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1, 3
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure 1, 2
• Do not add antipseudomonal coverage routinely—only when specific risk factors are present (structural lung disease, recent hospitalization with IV antibiotics, prior P. aeruginosa isolation) 4, 1
• Do not add MRSA coverage routinely—only when specific risk factors are present (prior MRSA infection, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates) 4, 1
• Do not extend therapy beyond 7 days in responding patients without specific indications (atypical pathogens, S. aureus, Gram-negative bacilli), as this increases antimicrobial resistance risk 4, 1