What are the recommended antibiotics for treating Community-Acquired Pneumonia (CAP)?

Community-Acquired Pneumonia Antibiotic Treatment

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

Outpatient Treatment

Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily is the preferred first-line agent, based on moderate quality evidence supporting effectiveness against common CAP pathogens 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin 1
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should only be used when local pneumococcal macrolide resistance is documented to be <25% 1, 2

Adults With Comorbidities or Recent Antibiotic Use

• Combination therapy is required: β-lactam (amoxicillin-clavulanate 2 g twice daily, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline 1, 3
• Alternative monotherapy option: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) 1, 4
• Fluoroquinolone use should be discouraged in uncomplicated cases due to FDA warnings about serious adverse events and resistance concerns 1

Inpatient Non-ICU Treatment

Two equally effective regimens exist with strong recommendations and high-quality evidence 1:

Preferred Combination Regimen

• 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, 5
• Administer the first antibiotic dose in the emergency department, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1

Alternative Monotherapy

• 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 1
• This is the preferred option for penicillin-allergic patients 1

ICU Treatment

Combination therapy is mandatory for all ICU patients 1:

• 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
• This regimen provides coverage against both typical and atypical pathogens with strong recommendation and level II evidence 1

Special Populations Requiring Broader Coverage

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage if patient has 1:

• Structural lung disease (bronchiectasis, COPD with frequent exacerbations)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of P. aeruginosa

Recommended regimen: Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus ciprofloxacin or levofloxacin, or alternative regimens with aminoglycoside plus azithromycin 1

MRSA Risk Factors

Add MRSA coverage if patient has 1:

• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics
• Post-influenza pneumonia
• Cavitary infiltrates on imaging

Recommended addition: Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) or linezolid 600 mg IV every 12 hours 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, 5
• Typical duration for uncomplicated CAP is 5-7 days 1
• Extend to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient meets all of the following criteria 1:

• Hemodynamically stable
• Clinically improving
• Able to take oral medications
• Normal gastrointestinal function

This typically occurs by day 2-3 of hospitalization 1

Recommended oral step-down regimen: Amoxicillin 1 g orally three times daily plus azithromycin 500 mg orally daily (or clarithromycin 500 mg orally twice daily as alternative macrolide) 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure 1
• Never delay antibiotic administration in hospitalized patients beyond 8 hours, as this increases mortality 1
• Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 1
• Do not use monotherapy in patients with comorbidities (including cardiovascular disease, COPD, diabetes, chronic kidney disease)—these patients require combination therapy or fluoroquinolone monotherapy 1, 3
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation 1
• Avoid extending therapy beyond 7 days in responding patients without specific indications, as this increases antimicrobial resistance risk 1

Multi-Drug Resistant Streptococcus pneumoniae (MDRSP)

For pneumococcal isolates with penicillin MIC ≥4 mg/L 6:

• Use respiratory fluoroquinolone (moxifloxacin has highest activity against S. pneumoniae, followed by gatifloxacin, then levofloxacin) 6
• Alternative options: vancomycin or clindamycin 6
• Consider ceftaroline 600 mg IV every 12 hours for MRSA and drug-resistant S. pneumoniae 6