Recommended Antibiotics for Cellulitis Treatment
For uncomplicated cellulitis, cephalexin 500 mg orally 4 times daily for 5-7 days is the first-line treatment, with alternatives including dicloxacillin, clindamycin, or amoxicillin-clavulanate. 1
Treatment Algorithm Based on Severity
Mild Cellulitis (limited area, no systemic symptoms)
- First-line: Cephalexin 500 mg orally 4 times daily for 5-7 days 1
- Alternatives:
- Dicloxacillin
- Clindamycin (300-450 mg orally three times daily)
- Amoxicillin-clavulanate (875/125 mg twice daily)
Moderate Cellulitis (more extensive or with systemic symptoms)
- First-line: Cephalexin 500 mg orally 4 times daily for 7-10 days 1
- If MRSA suspected: Add or substitute trimethoprim-sulfamethoxazole or clindamycin
Severe Cellulitis (extensive area, significant systemic symptoms)
- Hospitalization with IV antibiotics 1:
- Vancomycin
- Linezolid
- Daptomycin
- Empiric broad-spectrum coverage: Vancomycin plus piperacillin-tazobactam or a carbapenem
When to Suspect MRSA
Consider MRSA coverage if:
- History of prior MRSA infection
- Purulent drainage
- Failure to respond to beta-lactam therapy within 48-72 hours
- Patient is in a high-risk group: athletes, children, men who have sex with men, prisoners, military recruits, residents of long-term care facilities, intravenous drug users 2
Evidence Considerations
The Infectious Diseases Society of America (IDSA) guidelines strongly recommend cephalexin as first-line therapy for non-purulent cellulitis 1. This is based on the fact that most cases of cellulitis are caused by beta-hemolytic Streptococcus and methicillin-susceptible Staphylococcus aureus (MSSA) 2.
Research has shown that in areas with high MRSA prevalence, trimethoprim-sulfamethoxazole had higher success rates (91%) compared to cephalexin (74%) 3. However, the IDSA still recommends reserving MRSA coverage for specific situations rather than as first-line empiric therapy for all cellulitis cases 1.
Important Clinical Pearls
- Reevaluate patients within 48-72 hours to assess treatment response 1
- Elevation of the affected area reduces edema and aids healing 1
- Keep the area clean and dry; warm compresses may promote drainage 1
- Treatment duration: 5 days is typically sufficient, with extension if symptoms haven't improved 2
- Address predisposing factors to minimize risk of recurrence 2
Common Pitfalls to Avoid
- Failure to drain purulent collections when present - antibiotics alone are often insufficient for abscesses 1
- Inappropriate antibiotic selection or inadequate duration 1
- Missing necrotizing infections, which require immediate surgical consultation 1
- Overuse of broad-spectrum antibiotics - vancomycin and newer agents should be reserved for severe infections or confirmed MRSA 1
- Clindamycin carries risk of C. difficile colitis, though this is rare with short courses 1
Special Populations
- Children under 8 years: Cephalexin is preferred over doxycycline due to risk of dental staining with tetracyclines 1
- Beta-lactam allergy: Clindamycin 300-450mg orally three times daily for 5-6 days 1
- If both MRSA coverage and beta-lactam allergy: TMP-SMX (1-2 DS tablets twice daily) plus metronidazole (500mg three times daily) 1