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

Antibiotic Treatment for Community-Acquired Pneumonia

For outpatient CAP without comorbidities, amoxicillin 1 g three times daily is the preferred first-line therapy, while hospitalized patients should receive combination therapy with a β-lactam (ceftriaxone or cefotaxime) plus azithromycin, and ICU patients require intensified regimens with β-lactam plus either azithromycin or a respiratory fluoroquinolone. 1

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

• Amoxicillin 1 g three times daily is the first-line recommendation based on effectiveness against common CAP pathogens and moderate quality evidence 1
• Doxycycline 100 mg twice daily serves as an acceptable alternative when amoxicillin cannot be used 2, 1
• 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% 2, 1

Adults With Comorbidities

Comorbidities include chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppression; or recent antibiotic use within 3 months 2

Two equally effective options exist:

• Combination therapy: β-lactam (amoxicillin-clavulanate 2 g twice daily OR ceftriaxone OR cefpodoxime OR cefuroxime 500 mg twice daily) PLUS macrolide (azithromycin or clarithromycin) or doxycycline 2, 1
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin) 2, 1, 3, 4

Inpatient Non-ICU Treatment

Two regimens have strong evidence and equal efficacy:

• β-lactam (ceftriaxone 1-2 g daily OR cefotaxime 1-2 g every 8 hours OR ampicillin-sulbactam) PLUS azithromycin 500 mg daily 2, 1, 5
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) 2, 1, 3, 4

Key Clinical Points for Inpatients

• Administer the first antibiotic dose in the emergency department before admission to reduce mortality 1
• Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients 2, 1
• 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) 2, 1

ICU Treatment for Severe CAP

Combination therapy is mandatory for ICU patients:

• β-lactam (ceftriaxone 2 g daily OR cefotaxime 1-2 g every 8 hours OR ampicillin-sulbactam) PLUS either azithromycin 500 mg daily OR respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) 2, 1

Special ICU Considerations

For Pseudomonas aeruginosa risk factors (structural lung disease, recent hospitalization with parenteral antibiotics, prior respiratory isolation of P. aeruginosa, or recent broad-spectrum antibiotic use):

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

For MRSA risk factors (prior MRSA infection/colonization, recent hospitalization with parenteral antibiotics, cavitary infiltrates, or concurrent influenza):

• 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 1

Penicillin-Allergic Patients

• Outpatient: Respiratory fluoroquinolone or doxycycline 2, 1
• Inpatient non-ICU: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 2, 1
• ICU: Respiratory fluoroquinolone PLUS aztreonam 2 g IV every 8 hours 2, 1

Duration of Therapy

• Standard duration: 5-7 days for uncomplicated CAP once clinical stability is achieved 1
• Clinical stability criteria: temperature ≤37.8°C, heart rate ≤100 beats/min, respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mmHg, oxygen saturation ≥90%, ability to take oral medications, and normal mental status 2
• Extend to 14-21 days for Legionella, Staphylococcus aureus, or Gram-negative enteric bacilli 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this increases treatment failure risk 2, 1
• Avoid delaying antibiotic administration in hospitalized patients, as this increases mortality 1
• Do not automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors for resistant organisms 1
• Do not extend therapy beyond 7 days in responding patients without specific indications, as this increases antibiotic resistance risk 1
• Avoid using β-lactams other than ceftriaxone, cefotaxime, ampicillin-sulbactam, or piperacillin-tazobactam for hospitalized patients, as other agents have inferior outcomes 2

Diagnostic Testing Considerations

• Test all patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis affects treatment and infection prevention strategies 5
• Only 38% of hospitalized CAP patients have a pathogen identified; of those, up to 40% have viruses and approximately 15% have Streptococcus pneumoniae 5
• Expanded indications for blood and sputum cultures include all inpatients empirically treated for MRSA or P. aeruginosa 1