What is the first-line antibiotic for Community-Acquired Pneumonia (CAP)?

First-Line Antibiotic Treatment for Community-Acquired Pneumonia (CAP)

For outpatients with CAP without comorbidities, a macrolide (azithromycin or clarithromycin) or doxycycline is the recommended first-line antibiotic treatment. For outpatients with comorbidities or risk factors for drug-resistant pathogens, either a respiratory fluoroquinolone or a combination of a β-lactam plus a macrolide is recommended. 1

Outpatient Treatment

Previously Healthy Patients (No Risk Factors for Drug-Resistant S. pneumoniae)

• A macrolide (azithromycin or clarithromycin) is the first-line treatment 1
• Doxycycline is an alternative option 1

Patients with Comorbidities or Risk Factors

• A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg) 1
• OR a β-lactam plus a macrolide (high-dose amoxicillin 1g three times daily or amoxicillin-clavulanate 2g twice daily is preferred; alternatives include ceftriaxone, cefpodoxime, or cefuroxime) 1
• Doxycycline can be used as an alternative to macrolides in combination therapy 1

Inpatient Treatment (Non-ICU)

• A respiratory fluoroquinolone (levofloxacin, moxifloxacin) 1
• OR a β-lactam (cefotaxime, ceftriaxone, or ampicillin) plus a macrolide 1
• For penicillin-allergic patients, a respiratory fluoroquinolone is recommended 1

Important Considerations

• Recent research suggests respiratory fluoroquinolone monotherapy may have higher clinical cure rates (86.5% vs. 81.5%) and better microbiological eradication compared to β-lactam plus macrolide combinations, though mortality rates remain similar 2
• The FDA has approved levofloxacin specifically for CAP caused by susceptible strains of S. pneumoniae (including multi-drug resistant strains), H. influenzae, M. pneumoniae, and other common pathogens 3

Severe CAP (ICU Treatment)

• A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin or a respiratory fluoroquinolone 1
• For patients with risk factors for Pseudomonas: an antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin/levofloxacin or an aminoglycoside plus azithromycin 1

Duration of Treatment

• Treatment duration should generally not exceed 8 days in responding patients 1
• Short-course therapy (5 days) with high-dose levofloxacin (750 mg) has shown similar efficacy to standard 10-day regimens 3

Caveats and Special Considerations

• In regions with high rates (>25%) of macrolide-resistant S. pneumoniae, consider using alternative regimens even for patients without comorbidities 1
• Recent antibiotic use within the previous 3 months should prompt selection of an antibiotic from a different class 1
• A recent 2024 study found that adding macrolides to β-lactam therapy did not improve mortality outcomes or hospital length of stay in CAP patients, raising questions about the routine use of combination therapy 4
• Antibiotics should be initiated as soon as possible after diagnosis of CAP, particularly in patients with septic shock 1

Algorithm for First-Line Selection

1. Assess treatment setting (outpatient vs. inpatient vs. ICU)
2. Evaluate patient risk factors (comorbidities, recent antibiotic use, risk for drug-resistant pathogens)
3. For outpatients without risk factors: macrolide or doxycycline
4. For outpatients with risk factors: respiratory fluoroquinolone OR β-lactam plus macrolide
5. For inpatients (non-ICU): respiratory fluoroquinolone OR β-lactam plus macrolide
6. For severe CAP (ICU): β-lactam plus either azithromycin or respiratory fluoroquinolone

The choice between these regimens should be guided by local resistance patterns, patient allergies, and risk of adverse effects, with fluoroquinolones having more serious potential side effects but potentially higher cure rates as monotherapy 2, 1.