What are the recommended antibiotic treatments for community-acquired pneumonia (CAP)?

Antibiotic Treatment for Community-Acquired Pneumonia

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, use a β-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) plus either azithromycin or a respiratory fluoroquinolone. 1

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

• Amoxicillin 1 g three times daily is the preferred first-line agent based on effectiveness against common CAP pathogens and moderate quality evidence 1
• Doxycycline 100 mg twice daily serves as an acceptable alternative if amoxicillin is contraindicated 1
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily, or clarithromycin 500 mg twice daily) should only be used in geographic areas where pneumococcal macrolide resistance is documented to be <25% 1, 2

Adults With Comorbidities (COPD, diabetes, heart disease, renal disease, malignancy)

• Use combination therapy with a β-lactam plus either a macrolide or doxycycline 1
• β-lactam options include: amoxicillin-clavulanate, cefpodoxime, or cefuroxime 1
• Alternative: respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) provides equivalent efficacy with strong evidence 1, 3

Critical Pitfall for Outpatients

• Avoid macrolide monotherapy in areas with high pneumococcal resistance (>25%), as this significantly increases treatment failure risk 1
• Recent antibiotic exposure within 90 days should prompt selection of an alternative antibiotic class 1

Inpatient Non-ICU Treatment

Standard Regimen (Strong Recommendation, High Quality Evidence)

• Ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily is the preferred combination with the strongest evidence base 1, 2
• This regimen provides coverage for both typical pathogens (S. pneumoniae, H. influenzae) and atypical organisms (Mycoplasma, Chlamydia, Legionella) 1
• Administer the first antibiotic dose in the emergency department before hospital admission to reduce mortality 1

Alternative Regimen (Equally Effective)

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) has equivalent efficacy to β-lactam/macrolide combinations 1, 3
• This is the preferred option for penicillin-allergic patients 1

Transition to Oral Therapy

• Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving (defervescence, decreased oxygen requirement), able to take oral medications, and has normal GI function 1
• This typically occurs by hospital day 2-3 1

Critical Pitfall for Inpatients

• Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients to allow targeted de-escalation 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

ICU Treatment (Severe CAP)

Mandatory Combination Therapy

• 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 a respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• Combination therapy is mandatory for all ICU patients regardless of other factors 1

Penicillin-Allergic ICU Patients

• Use respiratory fluoroquinolone plus aztreonam 2 g IV every 8 hours 1

Special Situations Requiring Broader Coverage

Pseudomonas aeruginosa Risk Factors

Risk factors include: structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, prior respiratory isolation of P. aeruginosa, or recent broad-spectrum antibiotic use 1

Regimen for Pseudomonas coverage:

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

MRSA Risk Factors

Risk factors include: prior MRSA infection or colonization, recent hospitalization with IV antibiotics, cavitary infiltrates on imaging, or concurrent influenza 1

Add to base regimen:

• 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

• Standard duration is 5-7 days for uncomplicated CAP once clinical stability criteria are met 1
• Clinical stability criteria include: temperature ≤37.8°C, heart rate ≤100 bpm, respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mmHg, oxygen saturation ≥90% on room air, ability to take oral medications, and normal mental status 1
• Extend duration to 14-21 days for Legionella, Staphylococcus aureus, or Gram-negative enteric bacilli 1
• Do not extend therapy beyond 7 days in responding patients without specific indications, as this increases antimicrobial resistance risk 1

Key Clinical Considerations

Macrolide Resistance Patterns

• In areas where pneumococcal macrolide resistance exceeds 25%, avoid macrolide monotherapy entirely 1
• Local antibiogram data should guide empiric therapy selection 1

FDA-Approved Indications

• Levofloxacin is FDA-approved for both 5-day and 7-14 day treatment regimens for CAP, with the 5-day regimen excluding multi-drug resistant S. pneumoniae 3
• Azithromycin is FDA-approved at 500 mg day 1 followed by 250 mg daily for days 2-5 for CAP 2

Common Pitfalls to Avoid

• Never delay antibiotic administration in hospitalized patients—give the first dose in the emergency department 1
• Do not automatically escalate to broad-spectrum antibiotics without documented risk factors for resistant organisms 1
• Avoid β-lactam monotherapy for hospitalized patients, as this fails to cover atypical pathogens (Mycoplasma, Chlamydia, Legionella) that account for 10-40% of CAP cases 1, 4