What are the first-line antibiotics for community-acquired pneumonia?

First-Line Antibiotics for Community-Acquired Pneumonia

For community-acquired pneumonia (CAP), the first-line antibiotic treatment is a β-lactam (such as ceftriaxone, cefotaxime, or ampicillin-sulbactam) plus a macrolide (such as azithromycin), with respiratory fluoroquinolones (like levofloxacin) serving as an alternative regimen. 1

Treatment Algorithm Based on Setting

Outpatient Treatment

1. First choice:

   • Beta-lactam (e.g., amoxicillin 500-1000 mg every 8 hours) 2
   • OR macrolide (e.g., azithromycin 500 mg daily for 3 days or 500 mg on day 1 then 250 mg daily for 4 days) in areas with low rates of resistant Streptococcus pneumoniae 2
   • OR doxycycline (100 mg twice daily) in areas with low rates of resistant S. pneumoniae 2

2. Alternative options:

   • Beta-lactam + beta-lactamase inhibitor (e.g., amoxicillin-clavulanate) 2
   • OR second-generation fluoroquinolone (e.g., levofloxacin 500 mg daily) 3
   • OR cefuroxime axetil (750 mg twice daily) 2

Hospitalized Patients (Non-ICU)

1. First choice:

   • Second or third-generation cephalosporin (e.g., IV cefuroxime 750-1500 mg every 8 hours or IV ceftriaxone 1 g daily) PLUS a macrolide 2, 1
   • OR IV benzyl penicillin or IV amoxicillin PLUS a macrolide 2

2. Alternative option:

   • Respiratory fluoroquinolone monotherapy (e.g., levofloxacin 500-750 mg daily) 1, 3

ICU Patients

1. Without Pseudomonas risk:

   • Non-antipseudomonal cephalosporin + macrolide OR
   • Moxifloxacin or levofloxacin ± non-antipseudomonal cephalosporin 1

2. With Pseudomonas risk:

   • Antipseudomonal cephalosporin OR acylureidopenicillin/β-lactamase inhibitor OR carbapenem PLUS ciprofloxacin OR macrolide + aminoglycoside 1

Special Considerations

Pathogen-Specific Treatment

• For documented pneumococcal pneumonia: Beta-lactams have shown superior eradication rates (100%) compared to levofloxacin (44%) 4
• For atypical pathogens (Mycoplasma, Chlamydophila, Legionella): Macrolides or respiratory fluoroquinolones are highly effective 3, 5
• For MRSA: Consider adding vancomycin based on risk factors or positive nasal swab 1

Dosing Considerations

• Standard regimen: Levofloxacin 500 mg daily for 7-10 days 3, 6
• High-dose, short-course option: Levofloxacin 750 mg daily for 5 days - maximizes concentration-dependent activity and may improve compliance 6
• For severe CAP: Consider higher dosing (e.g., levofloxacin 500 mg twice daily) for patients requiring ICU admission 7

Treatment Duration

• Minimum duration: 5 days 1
• Continue until patient is afebrile for 48-72 hours and has no more than one sign of clinical instability 1
• Assess response at day 2-3 for hospitalized patients (fever, progression of infiltrates) 2
• Assess response at day 5-7 for outpatients (improvement of symptoms) 2

Switching from IV to Oral Therapy

Patients can be switched to oral therapy when they are:

• Hemodynamically stable
• Clinically improving
• Able to ingest medications
• Have a normally functioning gastrointestinal tract 1

Common Pitfalls to Avoid

1. Underestimating pneumococcal resistance: In areas with high rates of drug-resistant S. pneumoniae, avoid macrolide monotherapy 1
2. Overusing fluoroquinolones: Reserve for specific indications to prevent resistance development 1, 6
3. Inadequate coverage for atypical pathogens: Ensure coverage with either a macrolide or a respiratory fluoroquinolone 1
4. Prolonged IV therapy: Switch to oral therapy as soon as clinically appropriate to reduce hospital stay and complications 1, 8
5. Inappropriate duration: Treating longer than necessary increases risk of adverse effects and resistance 1

The combination of a third-generation cephalosporin and a macrolide has demonstrated equivalent or superior efficacy compared to fluoroquinolone monotherapy, with potential benefits for antimicrobial stewardship by reducing the development of resistant organisms 4, 8.