What is the recommended treatment for a patient with community-acquired pneumonia?

Treatment for Community-Acquired Pneumonia

For outpatients without comorbidities, start amoxicillin 1 g three times daily for 5-7 days; 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 ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily is required. 1

Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily is the preferred first-line therapy based on moderate quality evidence supporting effectiveness against common CAP pathogens including drug-resistant Streptococcus pneumoniae 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative, though this carries conditional recommendation with lower quality evidence 1
• Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented <25%, as resistance rates now exceed this threshold in most regions 1, 2
• Total duration: 5-7 days 1

Adults With Comorbidities (COPD, Diabetes, Heart/Liver/Renal Disease, Malignancy)

• Combination therapy is mandatory for this population 1
• Option 1 (Preferred): Amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily days 2-5 1
• Option 2: Respiratory fluoroquinolone monotherapy—levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily 1, 2
• Critical caveat: If patient used antibiotics within past 90 days, select agent from different antibiotic class to reduce resistance risk 1
• Total duration: 5-7 days 1

Hospitalized Non-ICU Patients

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

Regimen 1: β-lactam Plus Macrolide (Preferred)

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (IV or oral) 1
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours 1
• This combination provides coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1
• Combination therapy reduces mortality compared to β-lactam monotherapy, particularly in bacteremic pneumococcal pneumonia 3, 4

Regimen 2: Respiratory Fluoroquinolone Monotherapy

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1
• Systematic reviews demonstrate fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations 1
• Reserve for penicillin-allergic patients or when macrolides contraindicated 1

Transition to Oral Therapy

• Switch when patient is hemodynamically stable, clinically improving, afebrile for 48-72 hours, able to take oral medications, and has normal GI function—typically by day 2-3 1
• Oral step-down: amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily 1
• Alternative: continue respiratory fluoroquinolone orally at same dose 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease 1, 2:

Standard ICU 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 IV daily 1
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2
• The macrolide or fluoroquinolone component is essential for atypical pathogen coverage and has anti-inflammatory effects that reduce mortality in severe disease 3

Penicillin-Allergic ICU Patients

• Aztreonam 2 g IV every 8 hours PLUS respiratory fluoroquinolone 1

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage when ANY of these risk factors present 1:

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

Antipseudomonal regimen:

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

MRSA Risk Factors

Add MRSA coverage when ANY of these risk factors present 1, 2:

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

MRSA regimen:

• 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 base regimen 1

Duration of Therapy

• Minimum 5 days AND until patient afebrile for 48-72 hours with no more than one sign of clinical instability 1
• Typical duration for uncomplicated CAP: 5-7 days 1
• Extended duration (14-21 days) required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1
• Do NOT extend therapy beyond 7-8 days in responding patients without specific indications—longer courses increase antimicrobial resistance risk without improving outcomes 1

Critical Timing Considerations

• Administer first antibiotic dose immediately upon diagnosis, ideally while still in emergency department 1, 2
• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 1

Common Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1, 5
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—leads to treatment failure 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, QT prolongation) and resistance concerns 1, 6
• Do NOT automatically add broad-spectrum coverage (antipseudomonal or anti-MRSA) without documented risk factors—this increases resistance and C. difficile infection risk 1, 7
• Obtain blood and sputum cultures before initiating antibiotics in ALL hospitalized patients to allow pathogen-directed therapy 1

Diagnostic Testing for Hospitalized Patients

• Blood cultures (two sets from separate sites) 1
• Sputum Gram stain and culture (if productive cough) 1
• Urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1
• Consider urinary antigen for S. pneumoniae in severe cases 1

Clinical Stability Criteria Before Discharge

Patient must meet ALL of the following 1:

• Temperature ≤37.8°C (100°F)
• Heart rate ≤100 beats/min
• Respiratory rate ≤24 breaths/min
• Systolic blood pressure ≥90 mmHg
• Oxygen saturation ≥90% on room air
• Ability to maintain oral intake
• Normal mental status