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

Treatment for Community-Acquired Pneumonia

Outpatient Treatment (Healthy Adults Without Comorbidities)

Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy for previously healthy outpatients with community-acquired pneumonia. 1

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative, though this carries lower quality evidence 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 <25% 1, 2
• Avoid macrolide monotherapy in areas with high resistance rates (>25%), as this leads to treatment failure and breakthrough pneumococcal bacteremia 1

Outpatient Treatment (Adults With Comorbidities)

For patients with comorbidities (COPD, diabetes, chronic heart/liver/renal disease, malignancy) or recent antibiotic use within 3 months, use combination therapy with a β-lactam plus macrolide or respiratory fluoroquinolone monotherapy. 1

• Combination regimen: Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1
• Alternative β-lactams include cefpodoxime or cefuroxime, though these have inferior in vitro activity compared to high-dose amoxicillin 1
• Fluoroquinolone monotherapy: Levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily 1, 2
• However, avoid indiscriminate fluoroquinolone use in uncomplicated cases due to FDA warnings about serious adverse events and resistance concerns 1

Hospitalized Non-ICU Patients

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

Preferred Regimens:

• β-lactam plus macrolide: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily 1
• Alternative β-lactams: Cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours 1
• Fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1

Critical Timing:

• Administer the first antibiotic dose immediately in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1

Transition to Oral Therapy:

• Switch from IV to oral when 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 options: Amoxicillin 1 g three times daily or amoxicillin-clavulanate 875/125 mg twice daily, continuing azithromycin if initially used 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 1

Preferred Regimen:

• β-lactam PLUS macrolide or fluoroquinolone: 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 OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2
• This combination reduces mortality in critically ill patients with bacteremic pneumococcal pneumonia 1

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors:

Add antipseudomonal coverage only when specific risk factors are 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, cefepime, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 1

MRSA Risk Factors:

Add MRSA coverage only when specific risk factors are 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 the base regimen 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. 1

• Typical duration for uncomplicated CAP: 5-7 days 1, 2
• Extended duration (14-21 days) required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1
• Severe microbiologically undefined pneumonia: 10 days 1
• Avoid extending therapy beyond 7-8 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes 1

Penicillin-Allergic Patients

• Outpatient: Respiratory fluoroquinolone OR doxycycline 1
• Inpatient non-ICU: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• ICU: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily OR respiratory fluoroquinolone 1

Diagnostic Testing for Hospitalized Patients

Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in ALL hospitalized patients to allow pathogen-directed therapy and de-escalation. 1

• Urinary antigen testing for Legionella pneumophila serogroup 1 should be considered in severe CAP or ICU patients 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Never delay antibiotic administration—delays beyond 8 hours increase mortality 1
• Never use macrolides in areas where pneumococcal resistance exceeds 25%—leads to treatment failure 1
• Never automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors for Pseudomonas or MRSA 1
• Avoid oral cephalosporins (cefuroxime, cefpodoxime) as step-down therapy—these have inferior in vitro activity compared to high-dose amoxicillin 1

Azithromycin-Specific Warnings

Azithromycin carries FDA warnings for: 3

• QT prolongation and torsades de pointes—use caution in patients with known QT prolongation, bradyarrhythmias, uncorrected electrolyte abnormalities, or on QT-prolonging drugs 3
• Hepatotoxicity—discontinue immediately if signs of hepatitis occur 3
• Hypersensitivity reactions—including anaphylaxis and Stevens-Johnson syndrome 3
• C. difficile-associated diarrhea 3