What is the recommended treatment for community-acquired pneumonia (CAP)?

Community-Acquired Pneumonia Treatment

First-Line Empiric Therapy by Clinical Setting

Outpatient Treatment (Previously Healthy, No Comorbidities)

Amoxicillin 1 g orally three times daily is the preferred first-line therapy for healthy outpatients without comorbidities or recent antibiotic exposure. 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 in areas where pneumococcal macrolide resistance is documented to be <25% 2, 1
• The American Thoracic Society downgraded macrolide monotherapy from a strong to conditional recommendation based on rising resistance patterns 1

Outpatient Treatment (With Comorbidities or Recent Antibiotic Use)

Combination therapy with β-lactam plus macrolide or respiratory fluoroquinolone monotherapy is recommended for outpatients with comorbidities. 2, 1

• Combination regimen: Amoxicillin-clavulanate 2 g twice daily (or cefpodoxime or cefuroxime) plus azithromycin or clarithromycin 1
• Alternative monotherapy: Levofloxacin 750 mg daily or moxifloxacin 400 mg daily 2, 1
• Fluoroquinolone use should be reserved for specific situations due to FDA warnings about serious adverse events and resistance concerns 1

Inpatient Treatment (Non-ICU)

For hospitalized patients not requiring ICU admission, use either β-lactam plus macrolide combination or respiratory fluoroquinolone monotherapy—both carry strong recommendations with high-quality evidence. 2, 1

• Preferred combination: Ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily 2, 1, 3
• Alternative monotherapy: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 2, 1, 4
• For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative 1
• Administer the first antibiotic dose in the emergency department immediately upon diagnosis, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1, 5

Inpatient Treatment (ICU/Severe CAP)

Combination therapy with β-lactam plus either azithromycin or respiratory fluoroquinolone is mandatory for all ICU patients with severe CAP. 2, 1

• Preferred regimen: 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 daily 2, 1
• Alternative: β-lactam plus levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 2, 1
• For penicillin-allergic ICU patients, use respiratory fluoroquinolone plus aztreonam 2 g IV every 8 hours 1

Coverage for Drug-Resistant Pathogens

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage only when specific risk factors are present: structural lung disease, recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 2, 1

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

MRSA Risk Factors

Add vancomycin or linezolid only when MRSA risk factors are documented: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 2, 1

• MRSA coverage: Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) or linezolid 600 mg IV every 12 hours 2, 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; typical duration for uncomplicated CAP is 5-7 days. 2, 1, 5

• Extend duration to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 2, 1
• Short-course treatment (≤6 days) has equivalent clinical cure rates with fewer adverse events compared to ≥7 days 1

Transition from IV to Oral Therapy

Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization. 2, 1

• Oral step-down regimen: Amoxicillin 1 g orally three times daily plus azithromycin 500 mg orally daily (or clarithromycin 500 mg twice daily) 1
• For patients on fluoroquinolone monotherapy, continue the same agent orally at the same dose 1, 4

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure 2, 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 automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors for resistant organisms 1
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation 2, 1
• Avoid extending therapy beyond 7 days in responding patients without specific indications, as this increases antimicrobial resistance risk 1

Special Considerations

Adjunctive Corticosteroid Therapy

• Systemic corticosteroid administration within 24 hours of development of severe CAP may reduce 28-day mortality 5

Diagnostic Testing

• All patients with CAP should be tested for COVID-19 and influenza when these viruses are common in the community, as their diagnosis may affect treatment and infection prevention strategies 5

Follow-Up

• Clinical review should be arranged for all patients at approximately 6 weeks, either with their general practitioner or in a hospital clinic 2
• Chest radiograph at 6 weeks is reserved for patients with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1