What is the drug of choice for community-acquired pneumonia (CAP)?

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Last updated: October 31, 2025View editorial policy

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Drug of Choice for Community-Acquired Pneumonia

For community-acquired pneumonia (CAP), the drug of choice depends on patient setting, comorbidities, and risk factors, with a respiratory fluoroquinolone (levofloxacin, moxifloxacin) or a β-lactam plus macrolide combination being the preferred options for most hospitalized patients. 1, 2

Outpatient Treatment

Previously Healthy Adults (No Comorbidities)

  • A macrolide (azithromycin, clarithromycin, or erythromycin) is recommended as first-line therapy for previously healthy patients with no risk factors for drug-resistant S. pneumoniae 1, 2
  • Doxycycline is an acceptable alternative for patients without comorbidities 1, 2
  • Macrolide monotherapy should only be used in areas where pneumococcal resistance to macrolides is <25% 2

Patients with Comorbidities

  • A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg) is recommended for patients with comorbidities such as chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancies; asplenia; immunosuppression; or recent antibiotic use 1, 2
  • Alternatively, a β-lactam plus a macrolide combination can be used, with high-dose amoxicillin (1g three times daily) or amoxicillin-clavulanate (2g twice daily) as the preferred β-lactam options 1, 3
  • Alternative β-lactams include ceftriaxone, cefpodoxime, and cefuroxime 1

Inpatient Treatment (Non-ICU)

  • A respiratory fluoroquinolone (levofloxacin, moxifloxacin) as monotherapy is strongly recommended 1
  • Alternatively, a β-lactam plus a macrolide combination is equally effective 1
  • Preferred β-lactam agents include cefotaxime, ceftriaxone, and ampicillin; ertapenem can be used for selected patients with risk factors for gram-negative infections 1
  • For penicillin-allergic patients, a respiratory fluoroquinolone should be used 1

Inpatient Treatment (ICU)

  • A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin or a respiratory fluoroquinolone is strongly recommended 1
  • For penicillin-allergic patients, a respiratory fluoroquinolone plus aztreonam is recommended 1
  • For suspected Pseudomonas infection, an antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin/levofloxacin or an aminoglycoside and azithromycin is recommended 1
  • For suspected community-acquired MRSA, add vancomycin or linezolid to the regimen 1

Special Considerations

Drug Resistance

  • In regions with high rates (>25%) of macrolide-resistant S. pneumoniae, avoid macrolide monotherapy even in otherwise healthy patients 1, 2
  • Levofloxacin has been shown to be effective against macrolide-resistant S. pneumoniae 4
  • Recent antibiotic use increases the risk of drug-resistant pathogens; select an agent from a different class than what was recently used 1, 2

Treatment Duration

  • Standard duration of therapy is generally 5-7 days for uncomplicated CAP 2
  • Treatment should generally not exceed 8 days in a responding patient 1

Administration Timing

  • For hospitalized patients, the first antibiotic dose should be administered while still in the emergency department 1, 2
  • Antibiotic treatment should be initiated immediately after diagnosis of CAP 1

IV to Oral Switch

  • Hospitalized patients may be switched from intravenous to oral antibiotics after they show clinical improvement, are hemodynamically stable, and can tolerate oral medications 3

Pitfalls to Avoid

  • Avoid macrolide monotherapy in areas with high resistance rates or in patients with comorbidities 1, 2
  • Avoid delayed antibiotic administration in hospitalized patients as this can increase mortality risk 2
  • Don't overlook the possibility of atypical pathogens (Mycoplasma, Chlamydophila, Legionella) when selecting empiric therapy 5
  • Be cautious with fluoroquinolone use in patients with risk factors for prolonged QT interval or tendon disorders 3
  • Consider local resistance patterns when selecting empiric therapy, as these can vary significantly by region 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Antibiotic Regimen Recommendations for Community-Acquired Pneumonia in Adults

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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