Keflex (Cephalexin) for Uncomplicated Cellulitis
Cephalexin 500 mg orally four times daily for 5 days is a recommended first-line treatment for uncomplicated cellulitis, providing effective coverage against streptococci and methicillin-sensitive Staphylococcus aureus, which are the primary pathogens in typical cellulitis. 1
Evidence-Based Rationale
The Infectious Diseases Society of America (IDSA) and American College of Physicians endorse cephalosporins like cephalexin as first-line therapy for uncomplicated cellulitis 1. This recommendation is based on the microbiology of typical cellulitis, where streptococci (groups A, B, C, and G) are the predominant pathogens, with S. aureus being less common unless there is penetrating trauma or an underlying abscess 2.
Specific Dosing and Duration
- Standard dose: Cephalexin 500 mg orally four times daily 1
- Treatment duration: 5 days is as effective as 10 days if clinical improvement occurs within the first 5 days 2, 1
- High-dose option: Emerging evidence suggests cephalexin 1000 mg four times daily may reduce treatment failure rates (3.2% vs 12.9% with standard dosing), though with slightly more minor adverse effects 3
When Cephalexin Alone is Sufficient
Do NOT routinely add MRSA coverage to cephalexin for typical cellulitis. Multiple high-quality randomized controlled trials demonstrate that adding trimethoprim-sulfamethoxazole to cephalexin provides no additional benefit 4, 5. In the largest trial of 496 patients, clinical cure rates were identical: 83.5% with combination therapy versus 85.5% with cephalexin alone 4.
Standard beta-lactam therapy succeeds in 96% of typical cellulitis cases 1. MRSA is an unusual cause of non-purulent cellulitis 1.
When to Consider MRSA Coverage
Add MRSA coverage (trimethoprim-sulfamethoxazole, doxycycline, or clindamycin) ONLY if these specific features are present 1:
- Purulent drainage present
- Penetrating trauma or injection drug use
- Evidence of MRSA infection elsewhere or documented nasal colonization
- Systemic inflammatory response syndrome (SIRS)
- Failed initial beta-lactam therapy
Alternative Agents for Penicillin/Cephalexin Allergy
- Clindamycin 300-450 mg orally four times daily for 5 days is the preferred alternative for patients with cephalexin allergy 1, 6
- Clindamycin provides excellent streptococcal coverage and also covers MRSA if needed 6
Critical Adjunctive Measures
Beyond antibiotics, these interventions are essential 1, 6:
- Elevation of the affected limb to promote drainage of edema and inflammatory substances
- Treatment of predisposing conditions: tinea pedis (toe web infections), venous stasis dermatitis, lymphedema
- Skin hydration with emollients to prevent recurrence
Common Pitfalls to Avoid
Do not obtain cultures for typical cellulitis. Blood and tissue cultures are unnecessary for uncomplicated cases, as the pathogen isolation rate is less than 20% 2, 1. Reserve cultures for patients with malignancy, severe systemic features, or unusual predisposing factors 1.
Do not mistake purulent collections for cellulitis. Abscesses require drainage, not antibiotics alone 1. Consider point-of-care ultrasound if there is diagnostic uncertainty.
Expect possible initial worsening. Inflammation may temporarily increase after starting antibiotics due to pathogen destruction releasing inflammatory enzymes 2, 1. This does not indicate treatment failure.
When to Extend or Escalate Treatment
- Extend treatment beyond 5 days if no clinical improvement occurs within the first 5 days 1, 6
- Consider hospitalization for parenteral therapy if there is concern for deeper/necrotizing infection, severe immunocompromise, or outpatient treatment failure 6
FDA-Approved Indications
Cephalexin is FDA-approved for skin and skin structure infections caused by S. aureus and/or Streptococcus pyogenes 7, confirming its appropriateness for cellulitis treatment.