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

Community-Acquired Pneumonia Treatment

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

Outpatient Treatment

Previously Healthy Patients (No Comorbidities)

• Amoxicillin 1g orally three times daily is the preferred first-line therapy, based on strong recommendation and moderate quality evidence for effectiveness against common CAP pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis 1, 2

• Doxycycline 100mg twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries conditional recommendation with lower quality evidence 1, 2

• Macrolide monotherapy (azithromycin 500mg day 1, then 250mg daily; or clarithromycin 500mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented <25%, as resistance rates above this threshold lead to treatment failure 1, 2

Patients with Comorbidities or Recent Antibiotic Use

• Combination therapy with β-lactam (amoxicillin-clavulanate 2g twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) OR doxycycline is recommended for patients with chronic heart disease, lung disease, diabetes, renal insufficiency, malignancy, or recent antibiotic exposure within 90 days 1, 2

• Alternative monotherapy with respiratory fluoroquinolone (levofloxacin 750mg daily, moxifloxacin 400mg daily, or gemifloxacin 320mg daily) provides equivalent efficacy, though fluoroquinolone use should be reserved for specific situations due to FDA warnings about serious adverse events and resistance concerns 1, 2

Inpatient Non-ICU Treatment

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

Preferred Regimen: β-Lactam Plus Macrolide

• Ceftriaxone 1-2g IV daily PLUS azithromycin 500mg daily provides coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila) 1, 2, 3

• Alternative β-lactams include cefotaxime 1-2g IV every 8 hours or ampicillin-sulbactam 3g IV every 6 hours, always combined with azithromycin 1

• Recent evidence from a 2025 multicenter matched cohort study (n=5,342 matched pairs) demonstrated azithromycin was associated with lower in-hospital mortality (OR 0.71,95% CI: 0.56-0.9) and 90-day mortality (HR 0.83,95% CI: 0.73-0.95) compared to doxycycline when combined with β-lactams 4

Alternative Regimen: Respiratory Fluoroquinolone Monotherapy

• Levofloxacin 750mg IV daily OR moxifloxacin 400mg IV daily as monotherapy demonstrates equivalent efficacy to β-lactam/macrolide combinations with systematic reviews showing fewer clinical failures and treatment discontinuations 1, 2

• This regimen is preferred for penicillin-allergic patients 1

Critical Timing Consideration

• 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, 2

ICU/Severe CAP Treatment

Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate for severe disease:

Standard Severe CAP (No Pseudomonas/MRSA Risk)

• β-lactam (ceftriaxone 2g IV daily, cefotaxime 1-2g IV every 8 hours, or ampicillin-sulbactam 3g IV every 6 hours) PLUS either azithromycin 500mg IV daily OR respiratory fluoroquinolone (levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily) 1, 2, 5

Pseudomonas Risk Factors Present

Add antipseudomonal coverage if patient has:

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

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

MRSA Risk Factors Present

Add MRSA coverage if patient has:

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

• Add vancomycin 15mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600mg IV every 12 hours to the base regimen 1, 2

Systemic Corticosteroids for Severe CAP

• Systemic corticosteroid administration within 24 hours of severe CAP development may reduce 28-day mortality 3

Duration of Therapy

• Treat for a minimum of 5 days AND until patient is afebrile for 48-72 hours with no more than one sign of clinical instability, with typical duration for uncomplicated CAP being 5-7 days 1, 2, 5

• 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, normal mental status 1

• Extended duration of 14-21 days is required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2, 5

• Do NOT extend therapy beyond 7 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes 1

Transition from IV to Oral Therapy

Switch to oral antibiotics when ALL of the following criteria are met:

• Hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm)
• Clinically improving (decreasing fever, respiratory rate, oxygen requirements)
• Afebrile for 24-48 hours
• Able to take oral medications
• Normal gastrointestinal function
• Typically occurs by day 2-3 of hospitalization 1, 2, 5

Recommended Oral Step-Down Regimens

• Amoxicillin 1g orally three times daily PLUS azithromycin 500mg orally daily (or clarithromycin 500mg orally twice daily as alternative macrolide) 1

• Levofloxacin 750mg orally daily OR moxifloxacin 400mg orally daily for patients on fluoroquinolone monotherapy 1

• Note: Azithromycin's long tissue half-life allows for continued antimicrobial effect even after oral transition 1

Diagnostic Testing

• Obtain blood cultures and sputum cultures BEFORE initiating antibiotics in ALL hospitalized patients to allow pathogen-directed therapy and potential de-escalation 1, 2

• Test ALL patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis affects treatment (antiviral therapy) and infection prevention strategies 3

Follow-Up

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 1

• Scheduled clinical review at 6 weeks for ALL patients, with chest radiograph reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1, 5

• Chest radiograph is NOT required before hospital discharge in patients with satisfactory clinical recovery 1

Critical Pitfalls to Avoid

• NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as macrolide-resistant S. pneumoniae may also be resistant to doxycycline, leading to treatment failure 1, 2

• NEVER use macrolide monotherapy for hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1

• AVOID indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, CNS effects, QT prolongation) and resistance concerns 1, 6

• DO NOT use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas aeruginosa or MRSA are present, as these agents have inferior outcomes for standard CAP 1

• AVOID delayed antibiotic administration beyond 8 hours in hospitalized patients, as this increases 30-day mortality by 20-30% 1, 2

• DO NOT automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors for resistant organisms 1

• Be aware of azithromycin's serious adverse effects: QT prolongation (especially in elderly, those with cardiac disease, or on QT-prolonging drugs), hepatotoxicity, Clostridioides difficile infection, and hypersensitivity reactions including Stevens-Johnson syndrome 6

• Exercise caution with azithromycin in patients with: known QT prolongation, history of torsades de pointes, congenital long QT syndrome, bradyarrhythmias, uncompensated heart failure, uncorrected hypokalemia/hypomagnesemia, or concurrent use of Class IA/III antiarrhythmics 6