Community-Acquired Pneumonia Treatment
Outpatient Management
Previously Healthy Adults (No Comorbidities)
Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line therapy, providing superior pneumococcal coverage against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains 1, 2.
Doxycycline 100 mg orally twice daily for 5–7 days serves as an acceptable alternative when amoxicillin is contraindicated, offering coverage of both typical and atypical pathogens 1, 2.
Macrolide monotherapy (azithromycin 500 mg day 1 then 250 mg daily, or clarithromycin 500 mg twice daily) should only be used when local pneumococcal macrolide resistance is documented <25%; in most U.S. regions resistance is 20–30%, making this approach unsafe as first-line therapy 1, 2.
Patients with Comorbidities or Recent Antibiotic Use
For adults with chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia; immunosuppression; or antibiotic use within 90 days, combination therapy is required 1, 2.
Option 1 – Combination therapy: Amoxicillin-clavulanate 875 mg/125 mg (or 2000 mg/125 mg) orally twice daily PLUS azithromycin 500 mg day 1 then 250 mg daily (or clarithromycin 500 mg twice daily or doxycycline 100 mg twice daily) for 5–7 days 1, 2.
Alternative β-lactams include cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily, always combined with a macrolide or doxycycline 1.
Option 2 – Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg orally once daily OR moxifloxacin 400 mg orally once daily OR gemifloxacin 320 mg orally once daily for 5–7 days 1, 2.
Fluoroquinolones should be reserved for patients with β-lactam allergy or contraindications to combination therapy due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance 1, 2.
Hospitalized Patients (Non-ICU)
Two equally effective regimens exist with strong recommendations and high-quality evidence 1, 2:
Preferred Regimen 1: β-lactam Plus Macrolide
Ceftriaxone 1–2 g IV once daily PLUS azithromycin 500 mg IV or orally daily provides comprehensive coverage for typical pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1, 2, 3.
Alternative β-lactams include cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 1, 2.
This combination reduces mortality compared with β-lactam monotherapy in hospitalized patients 1, 2, 3.
Preferred Regimen 2: Respiratory Fluoroquinolone Monotherapy
Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily as monotherapy is equally effective as β-lactam/macrolide combinations 1, 2.
Fluoroquinolone monotherapy is reserved for penicillin-allergic patients or when combination therapy is contraindicated 1, 2.
Critical Timing and Diagnostic Measures
Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30% 1, 2, 3.
Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation 1, 2.
Intensive Care Unit (Severe CAP)
Combination therapy is mandatory for all ICU patients; β-lactam monotherapy is associated with higher mortality in critically ill patients with bacteremic pneumococcal pneumonia 1, 2, 3.
Standard ICU Regimen
Ceftriaxone 2 g IV once 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 a respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2.
For penicillin-allergic ICU patients, use aztreonam 2 g IV every 8 hours PLUS a respiratory fluoroquinolone 1.
ICU Admission Criteria
- One major criterion (septic shock requiring vasopressors OR respiratory failure requiring mechanical ventilation) OR ≥3 minor criteria (confusion, respiratory rate ≥30/min, systolic BP <90 mmHg, multilobar infiltrates, PaO₂/FiO₂ <250) 1, 2.
Special Pathogen Coverage (Risk Factor-Based)
Pseudomonas aeruginosa Coverage
Add antipseudomonal therapy ONLY when specific risk factors are present 1, 2:
- Structural lung disease (bronchiectasis, cystic fibrosis)
- Recent hospitalization with IV antibiotics within 90 days
- Prior respiratory isolation of P. aeruginosa
- Chronic broad-spectrum antibiotic exposure (≥7 days in past month)
Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours OR imipenem OR meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS an aminoglycoside (gentamicin or tobramycin 5–7 mg/kg IV daily) for dual coverage 1, 2.
MRSA Coverage
Add MRSA therapy ONLY when specific risk factors are present 1, 2:
- Prior MRSA infection or colonization
- Recent hospitalization with IV antibiotics within 90 days
- Post-influenza pneumonia
- Cavitary infiltrates on imaging
Regimen: Vancomycin 15 mg/kg IV every 8–12 hours (target trough 15–20 µg/mL) OR linezolid 600 mg IV every 12 hours, added to the base CAP regimen 1, 2.
Duration of Therapy
Minimum treatment duration: 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability 1, 2, 3.
Extended duration (14–21 days) is required ONLY for infections caused by Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2.
Transition from IV to Oral Therapy
Switch to oral antibiotics when all clinical stability criteria are met 1, 2, 3:
- Hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm)
- Clinically improving
- Afebrile for 48–72 hours
- Respiratory rate ≤24 breaths/min
- Oxygen saturation ≥90% on room air
- Able to take oral medications
- Normal gastrointestinal function
Transition typically occurs by hospital day 2–3 1, 2, 3.
Oral step-down options include amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily (or azithromycin alone after 2–3 days of IV therapy) 1, 2.
Adjunctive Care
Supportive Measures
Oxygen therapy targeting PaO₂ >8 kPa (60 mmHg) and SpO₂ >92% in all patients with hypoxemia 2.
Monitor temperature, respiratory rate, pulse, blood pressure, mental status, and oxygen saturation at least twice daily in hospitalized patients 1, 2.
Evaluate for volume depletion and consider IV fluids as needed 2.
Corticosteroids
- Systemic corticosteroid administration within 24 hours of severe CAP development may reduce 28-day mortality in ICU patients 3.
Vaccination and Prevention
Administer pneumococcal polysaccharide vaccine to all patients ≥65 years and those with high-risk conditions (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia; immunosuppression) 1, 2.
Recommend annual influenza vaccination for all patients, especially those with chronic medical illnesses 1, 2.
Provide smoking cessation counseling to all current smokers 1, 2.
Critical Pitfalls to Avoid
Never use macrolide monotherapy in hospitalized patients—it fails to cover typical pathogens like S. pneumoniae and leads to treatment failure 1, 2.
Never use macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25% (the situation in most U.S. regions) 1, 2.
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA safety warnings and resistance concerns 1, 2.
Do not add broad-spectrum antipseudomonal or MRSA agents routinely—restrict their use to patients with documented risk factors to prevent unnecessary resistance, adverse effects, and cost 1, 2.
Do not delay antibiotic administration beyond 8 hours—this increases 30-day mortality by 20–30% in hospitalized patients 1, 2, 3.
Do not extend therapy beyond 7–8 days in responding patients without specific indications—longer courses increase antimicrobial resistance risk without improving outcomes 1, 2.
Obtain blood and sputum cultures before starting antibiotics in all hospitalized patients—this enables pathogen-directed therapy and safe de-escalation 1, 2.