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

Antibiotic Treatment for Community-Acquired Pneumonia (CAP)

For healthy outpatients without comorbidities, amoxicillin 1 g three times daily is the preferred first-line antibiotic, with doxycycline 100 mg twice daily as an acceptable alternative. 1

Outpatient Treatment

Healthy Adults Without Comorbidities

• Amoxicillin 1 g three times daily is the first-line choice (strong recommendation, moderate quality evidence) 1
• Doxycycline 100 mg twice daily serves as an alternative (conditional recommendation, low 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 <25% 1, 2

Critical pitfall: Avoid macrolide monotherapy in regions with high resistance rates (≥25%), as this significantly increases treatment failure risk 1, 2

Outpatients With Comorbidities

Comorbidities include: chronic heart/lung/liver/renal disease, diabetes mellitus, alcoholism, malignancy, or asplenia 1

Two equally effective options:

Option 1 - Combination therapy (strong recommendation): 1

• β-lactam: amoxicillin/clavulanate 500/125 mg three times daily OR 875/125 mg twice daily OR cefpodoxime 200 mg twice daily OR cefuroxime 500 mg twice daily
• PLUS macrolide (azithromycin or clarithromycin) OR doxycycline 100 mg twice daily 1

Option 2 - Monotherapy (strong recommendation): 1

• Respiratory fluoroquinolone: levofloxacin 750 mg daily OR moxifloxacin 400 mg daily OR gemifloxacin 320 mg daily 1, 2

Inpatient Treatment (Non-ICU)

For hospitalized patients not requiring ICU admission, use either β-lactam plus macrolide OR respiratory fluoroquinolone monotherapy (both strong recommendations, high quality evidence) 1, 2

Preferred Regimens:

Option 1 - Combination therapy: 1, 2

• β-lactam: ceftriaxone 1-2 g daily OR cefotaxime 1-2 g every 8 hours OR ampicillin-sulbactam 3 g every 6 hours
• PLUS azithromycin 500 mg daily OR clarithromycin 500 mg twice daily 1

Option 2 - Monotherapy: 1, 2

• Levofloxacin 750 mg daily OR moxifloxacin 400 mg daily 2, 3

Alternative for specific contraindications: 1, 2

• β-lactam plus doxycycline 100 mg twice daily (conditional recommendation, lower quality evidence)

Key practice point: Administer the first antibiotic dose while still in the emergency department, as delayed administration increases mortality 2

ICU Treatment (Severe CAP)

For severe CAP requiring ICU admission, use β-lactam plus either azithromycin OR respiratory fluoroquinolone (strong recommendation) 1, 2

Standard Regimen:

• β-lactam: ceftriaxone 2 g daily OR cefotaxime 1-2 g every 8 hours OR ampicillin-sulbactam 3 g every 6 hours OR ceftaroline 600 mg every 12 hours
• PLUS azithromycin 500 mg daily OR levofloxacin 750 mg daily OR moxifloxacin 400 mg daily 1, 2

Special Situations Requiring Broader Coverage:

For suspected Pseudomonas aeruginosa (risk factors: structural lung disease, recent hospitalization with IV antibiotics, prior P. aeruginosa isolation, recent broad-spectrum antibiotic use): 2

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem)
• PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg daily
• PLUS azithromycin 500 mg daily 1, 2

For suspected MRSA (risk factors: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, cavitary infiltrates, concurrent influenza): 2

• Add vancomycin 15-20 mg/kg every 8-12 hours OR linezolid 600 mg every 12 hours to the base regimen 1, 2

Critical pitfall: Do NOT automatically escalate to broad-spectrum antibiotics (vancomycin, piperacillin-tazobactam) without documented risk factors, as this was common in practice but increases C. difficile risk and resistance 4

Duration of Therapy

Treat for a minimum of 5 days and until the patient achieves clinical stability (defined as: temperature ≤37.8°C, heart rate ≤100/min, respiratory rate ≤24/min, systolic BP ≥90 mmHg, oxygen saturation ≥90%, ability to take oral medications, normal mental status) 2, 5

• Standard duration: 5-7 days for uncomplicated CAP 2
• Extend to 14-21 days for Legionella, Staphylococcus aureus, or Gram-negative enteric bacilli 1
• Do NOT extend beyond 7 days in responding patients without specific indications, as this increases resistance risk 2

Transition to Oral Therapy

Switch from IV to oral antibiotics when: 2

• Hemodynamically stable
• Clinically improving
• Able to take oral medications
• Normal GI function
• Typically by day 2-3 of hospitalization 2

Penicillin-Allergic Patients

• Outpatient: Respiratory fluoroquinolone OR doxycycline 1
• Inpatient non-ICU: Respiratory fluoroquinolone monotherapy 1, 2
• ICU: Respiratory fluoroquinolone plus aztreonam 2

Multi-Drug Resistant S. pneumoniae (MDRSP)

MDRSP is defined as resistance to ≥2 of: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins, macrolides, tetracyclines, trimethoprim-sulfamethoxazole 1, 3

Treatment: 6

• Respiratory fluoroquinolone (moxifloxacin preferred for highest pneumococcal activity, then levofloxacin) 6, 7
• OR ceftaroline 600 mg IV every 12 hours 6
• Levofloxacin achieved 95% clinical and bacteriologic success in MDRSP cases 3

Important Caveats

• Avoid selecting an antibiotic from the same class if the patient received antibiotics within the previous 3 months, as this increases resistance risk 2, 5
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow targeted de-escalation 2
• In areas with high macrolide resistance (≥25%), avoid macrolide monotherapy even for healthy outpatients 1, 2, 5
• The 2019 guidelines abandoned the healthcare-associated pneumonia (HCAP) category; base decisions on local epidemiology and validated risk factors for MRSA/Pseudomonas rather than recent healthcare contact alone 2