What antibiotics are used to treat Community-Acquired Pneumonia (CAP)?

Antibiotic Treatment for Community-Acquired Pneumonia

For outpatient CAP in otherwise healthy adults, amoxicillin 1 g three times daily is the preferred first-line therapy, while hospitalized non-ICU patients should receive ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily, and ICU patients require mandatory combination therapy with a β-lactam plus either azithromycin or a respiratory fluoroquinolone. 1

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily is the preferred first-line agent based on effectiveness against common CAP pathogens and moderate quality evidence 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative (conditional recommendation) 1
• Macrolides should ONLY be used in areas where pneumococcal macrolide resistance is <25% 1, 2
  • Azithromycin 500 mg on day 1, then 250 mg daily 1
  • Clarithromycin 500 mg twice daily 1

Adults With Comorbidities (Diabetes, Heart Disease, Liver Disease, Renal Disease)

Two equally effective options: 1

1. Combination therapy: β-lactam (amoxicillin-clavulanate, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) OR doxycycline 1

2. Respiratory fluoroquinolone monotherapy: 1, 3

   • Levofloxacin 750 mg daily
   • Moxifloxacin 400 mg daily
   • Gemifloxacin 320 mg daily

Inpatient Non-ICU Treatment

Two guideline-recommended regimens with strong evidence and equal efficacy: 1

Primary Regimen (Preferred)

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV daily (strong recommendation, high quality evidence) 1
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours 1

Alternative Regimen

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) 1, 3

For Penicillin-Allergic Patients

• Respiratory fluoroquinolone (levofloxacin or moxifloxacin) 1
• Alternative: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily (if fluoroquinolone contraindicated) 1

ICU Treatment (Severe CAP)

Combination therapy is MANDATORY for all ICU patients: 1, 2

Standard ICU Regimen

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

Risk Factors for Pseudomonas Aeruginosa

If present, escalate to antipseudomonal coverage: 1, 2

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

Antipseudomonal regimen: 2, 1

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

Risk Factors for MRSA

If present, add MRSA coverage: 1

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

MRSA regimen additions: 1

• Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) 1
• OR Linezolid 600 mg IV every 12 hours 1

Duration of Therapy

Standard Duration

• Minimum 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 1, 2
• Typical duration: 5-7 days for uncomplicated CAP 1, 2
• Evidence shows short-course treatment (≤6 days) has equivalent clinical cure rates with fewer adverse events compared to ≥7 days 2

Extended Duration (14-21 Days)

Required for specific pathogens: 1

• Legionella pneumophila
• Staphylococcus aureus
• Gram-negative enteric bacilli
• Extrapulmonary complications (empyema, meningitis)

Transition to Oral Therapy

Switch from IV to oral when ALL criteria met: 1

• Hemodynamically stable
• Clinically improving
• Able to ingest oral medications
• Normal gastrointestinal function
• Typically by day 2-3 of hospitalization 1

Oral step-down regimens: 1

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 1
• OR Respiratory fluoroquinolone (levofloxacin 750 mg orally daily OR moxifloxacin 400 mg orally daily) 1

Critical Timing Considerations

Administer the first antibiotic dose in the emergency department IMMEDIATELY upon diagnosis 1, 2

• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 2, 1
• This represents a strong recommendation with level I evidence 1

Common Pitfalls to Avoid

Macrolide Resistance

• NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25% 1
• Macrolide-resistant S. pneumoniae may also be resistant to doxycycline 2
• Real-world data shows 35% of otherwise healthy patients inappropriately received broad-spectrum antibiotics not recommended by guidelines 4

Inappropriate Broad-Spectrum Use

• Do NOT automatically escalate to antipseudomonal or anti-MRSA coverage without documented risk factors 1
• Obtain blood and sputum cultures before initiating antibiotics in ALL hospitalized patients to allow targeted de-escalation 1

Duration Errors

• Do NOT extend therapy beyond 7 days in responding patients without specific indications (increases resistance risk) 2, 1
• Ten-day courses remain common in practice despite evidence supporting shorter durations 4

β-Lactam Selection Errors

• Avoid cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 1
• Ceftriaxone and cefotaxime are the preferred β-lactams for standard CAP treatment 1

Follow-Up and Monitoring

Reassessment at 48-72 Hours

If no clinical improvement: 1

• Repeat chest radiograph
• Repeat inflammatory markers (CRP, white blood cell count)
• Obtain additional microbiological specimens
• Consider changing antibiotic regimen (add or substitute macrolide, switch to fluoroquinolone, or add rifampicin) 1

Six-Week Follow-Up

• Schedule clinical review at 6 weeks for all hospitalized patients 1
• Obtain follow-up chest radiograph at 6 weeks for: 1, 5
  • Persistent symptoms or physical signs
  • Smokers over 50 years (higher risk for underlying malignancy)
  • Patients with increased risk factors for malignancy
• Chest radiograph is NOT required before hospital discharge in patients with satisfactory clinical recovery 1