Best Antibiotics for Cellulitis
For non-purulent cellulitis, cephalexin 500 mg orally 4 times daily for 5-7 days is the first-line treatment, targeting β-hemolytic streptococci which are the primary causative organisms. 1
First-Line Treatment Options
Mild to Moderate Non-Purulent Cellulitis
- First choice: Cephalexin 500 mg orally 4 times daily for 5-7 days 1
- Alternative options (if allergic to cephalosporins):
- Dicloxacillin
- Clindamycin 300-450 mg orally three times daily
- Amoxicillin-clavulanate 875/125 mg twice daily 1
Duration of Treatment
- 5 days is sufficient for uncomplicated cellulitis 1, 2
- Research confirms that a 5-day course of antibiotics is as effective as a 10-day course for uncomplicated cellulitis (98% success rate in both groups) 2
- Treatment can be extended if symptoms are not improved after 5 days 1
When to Consider MRSA Coverage
MRSA coverage should be considered in specific situations:
- History of prior MRSA infection
- Purulent drainage
- Failure to respond to beta-lactam therapy within 48-72 hours 1
MRSA Coverage Options
- Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 DS tablets twice daily
- Doxycycline 100 mg twice daily
- Clindamycin 300-450 mg orally three times daily
- Linezolid 600 mg twice daily 1
Combination Therapy Considerations
Research has shown that adding TMP-SMX to cephalexin does not significantly improve outcomes for uncomplicated cellulitis:
- In a per-protocol analysis, clinical cure occurred in 83.5% with combination therapy vs 85.5% with cephalexin alone 3
- Another study found no benefit of adding TMP-SMX to cephalexin (85% cure with combination vs 82% with cephalexin alone) 4
However, in areas with high prevalence of community-associated MRSA:
- TMP-SMX showed significantly higher success rates compared to cephalexin (91% vs 74%) 5
- Clindamycin showed higher success rates than cephalexin in patients with confirmed MRSA infections 5
Severe Infections Requiring Hospitalization
For severe infections requiring IV antibiotics:
- Vancomycin
- Linezolid 600 mg IV twice daily
- Daptomycin 4 mg/kg IV once daily
- Telavancin 10 mg/kg IV once daily
- Clindamycin 600 mg IV three times daily 1
Special Populations
Children
- Cephalexin is preferred for children under 8 years
- Avoid tetracyclines in children <8 years due to dental staining risk 1
Beta-lactam Allergic Patients
- Clindamycin 300-450mg orally three times daily for 5-6 days
- Alternative: TMP-SMX plus metronidazole if MRSA is suspected 1
Common Pitfalls to Avoid
Inadequate treatment duration: Extend therapy if clinical response is inadequate after initial course 1
Failure to drain purulent collections: Antibiotics alone are often insufficient for abscesses 1
Inappropriate antibiotic selection: Ensure coverage of the most likely pathogens (primarily β-hemolytic streptococci for non-purulent cellulitis) 1
Overuse of broad-spectrum antibiotics: Reserve vancomycin and newer agents for severe infections or confirmed MRSA 1
Missing necrotizing infections: These require immediate surgical consultation 1
Supportive Care
- Elevate the affected area to reduce edema
- Keep the area clean and dry
- Apply warm compresses to promote drainage
- Consider daily cleansing with chlorhexidine or povidone-iodine solution 1
Follow-up Recommendations
Patients should be reevaluated within 48-72 hours to assess treatment response. Consider MRSA coverage if no improvement is seen within this timeframe 1.