When do you use azithromycin vs amoxicillin vs doxycycline vs levofloxacin vs cephalexin (Keflex)?

Antibiotic Selection Guide: Azithromycin vs Amoxicillin vs Doxycycline vs Levofloxacin vs Cephalexin (Keflex)

The choice between azithromycin, amoxicillin, doxycycline, levofloxacin, and cephalexin should be based on the specific infection type, suspected pathogen, and resistance patterns, with fluoroquinolones like levofloxacin reserved only for situations where other options cannot be used due to their serious side effect profile. 1

Skin and Soft Tissue Infections

First-line options:

• Dicloxacillin or cephalexin (Keflex): For uncomplicated skin infections like impetigo, cellulitis, or minor abscesses caused by methicillin-susceptible Staphylococcus aureus (MSSA) 1
• Amoxicillin-clavulanate: For mixed infections or when beta-lactamase producing organisms are suspected 1

Alternative options:

• Clindamycin: For penicillin-allergic patients or MRSA coverage 1
• Doxycycline: Alternative for MRSA coverage in adults (not recommended for children under 8 years) 1
• Azithromycin: Short-course therapy (5 days) has shown comparable efficacy to cephalexin (10 days) for skin infections 2, 3

Respiratory Tract Infections

Community-Acquired Pneumonia

• First-line: Amoxicillin or amoxicillin-clavulanate 1
• Second-line: Doxycycline or cephalexin 1
• For atypical pathogens:
  • Mycoplasma pneumoniae: Doxycycline preferred; azithromycin as alternative 1
  • Chlamydophila pneumoniae: Azithromycin preferred; doxycycline as alternative 1
  • Legionella species: Levofloxacin or azithromycin 1

COPD Exacerbations

• First-line: Amoxicillin or amoxicillin-clavulanate (only if purulent sputum or evidence of pneumonia) 1
• Second-line: Doxycycline or cephalexin 1
• Note: Levofloxacin should be reserved for cases where first and second-line options cannot be used due to potential serious side effects 1

Gastrointestinal Infections

Travelers' Diarrhea

• First-line for dysentery: Azithromycin (single 1g dose or 500mg daily for 3 days) 1
• For watery diarrhea: Fluoroquinolones (like levofloxacin), azithromycin, or rifaximin have shown equivalent efficacy 1
• Note: Azithromycin is preferred over fluoroquinolones in regions with high rates of fluoroquinolone-resistant Campylobacter 1

Genitourinary Infections

Prostatitis

• For chlamydial prostatitis: Azithromycin shows better eradication and clinical cure rates compared to ciprofloxacin 4
• For ureaplasmal prostatitis: Doxycycline or azithromycin (similar efficacy) 4

Special Considerations

Antibiotic Allergies

• Penicillin/cephalosporin allergy: Azithromycin is generally safe in patients with beta-lactam allergies 5

Side Effect Profiles

• Gastrointestinal effects: All five antibiotics can cause nausea/vomiting, with cefixime having the highest rate of diarrhea (9.2 per 1000 patients) 6
• Fluoroquinolones (levofloxacin): Associated with potentially permanent side effects affecting tendons, muscles, joints, peripheral nerves, and central nervous system. Should be reserved for serious infections where benefits outweigh risks 1

Common Pitfalls to Avoid

1. Overuse of fluoroquinolones: Levofloxacin should not be used as first-line therapy due to serious side effects and increasing resistance 1

2. Inappropriate duration: Short-course therapy with azithromycin (5 days) can be as effective as longer courses of other antibiotics (e.g., 10 days of cephalexin) for certain infections 2, 3

3. Ignoring local resistance patterns: Regional antibiotic resistance should guide empiric therapy, particularly for fluoroquinolones and macrolides

4. Failure to adjust for specific pathogens:

   • For Streptococcus pneumoniae with penicillin MIC ≥2, use cefotaxime, ceftriaxone, fluoroquinolones, or high-dose amoxicillin 1
   • For MRSA, use vancomycin, teicoplanin, or linezolid rather than beta-lactams 1

5. Overlooking atypical pathogens: For suspected atypical pneumonia pathogens, doxycycline or azithromycin are more appropriate than amoxicillin or cephalexin 1

By following these guidelines and considering the specific infection type, suspected pathogen, and patient factors, clinicians can make appropriate choices among these commonly used antibiotics to optimize treatment outcomes while minimizing adverse effects.