Treatment Duration for Lower Extremity Cellulitis with Keflex (Cephalexin)
Treat uncomplicated lower extremity cellulitis with cephalexin for 5 days if clinical improvement has occurred, extending only if symptoms have not improved within this timeframe. 1
Evidence Supporting 5-Day Duration
The Infectious Diseases Society of America establishes 5 days as the standard treatment duration for cellulitis, representing a significant departure from traditional 7-14 day courses that are no longer necessary for uncomplicated cases. 1 This recommendation is supported by a randomized controlled trial demonstrating that 5 days of antibiotic therapy achieved 98% cure rates, equivalent to 10-day courses. 2
Clinical Algorithm for Treatment Duration
Initial 5-Day Course:
- Start cephalexin 500 mg orally four times daily 3
- Reassess at 48-72 hours to verify clinical response 1
- If clear improvement is evident by day 5, discontinue antibiotics 1
Extension Beyond 5 Days:
- Continue treatment only if erythema is still spreading or systemic symptoms persist 1
- Reassess for alternative diagnoses (necrotizing fasciitis, abscess, DVT) if no improvement by 48 hours 1
- Consider MRSA coverage if treatment failure occurs despite adequate beta-lactam therapy 1
Why Cephalexin is Appropriate for Lower Extremity Cellulitis
Beta-lactam monotherapy succeeds in 96% of typical cellulitis cases, confirming that MRSA coverage is unnecessary for standard presentations. 1 Cephalexin provides excellent coverage against beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus, the primary pathogens in nonpurulent cellulitis. 1
Critical Pitfalls to Avoid
Do not reflexively extend treatment to 7-10 days out of habit. The evidence clearly demonstrates that 5 days is sufficient when clinical improvement occurs. 1 Prolonging therapy unnecessarily increases adverse effects, costs, and antibiotic resistance without improving outcomes.
Do not add MRSA coverage (such as trimethoprim-sulfamethoxazole) to cephalexin for typical nonpurulent cellulitis. A randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no benefit over cephalexin alone, with cure rates of 85% versus 82% respectively. 4
Reassess within 48 hours if symptoms worsen or fail to improve. Treatment failure rates of approximately 20% occur with oral regimens, necessitating early reassessment for complications or resistant organisms. 5
When MRSA Coverage IS Needed
Add MRSA-active antibiotics only when specific risk factors are present: 1
- Penetrating trauma or injection drug use
- Purulent drainage or exudate
- Known MRSA colonization or prior MRSA infection
- Systemic inflammatory response syndrome (SIRS)
- Failure of beta-lactam therapy after 48 hours
For these cases, use combination therapy with trimethoprim-sulfamethoxazole plus cephalexin, doxycycline plus cephalexin, or clindamycin monotherapy. 1
Adjunctive Measures That Accelerate Recovery
Elevate the affected extremity to promote gravitational drainage of edema and inflammatory mediators, which hastens clinical improvement. 1
Identify and treat predisposing conditions including: 3
- Tinea pedis and toe web abnormalities
- Venous insufficiency and lymphedema
- Chronic edema and obesity
These interventions should be performed during the acute stage and as part of routine follow-up to prevent recurrence. 3
Hospitalization Criteria
Admit patients with any of the following: 1
- Systemic inflammatory response syndrome (fever, tachycardia, hypotension)
- Altered mental status or severe systemic toxicity
- Suspected necrotizing fasciitis (severe pain out of proportion to exam, rapid progression, skin anesthesia)
- Severe immunocompromise or neutropenia
For hospitalized patients requiring IV therapy, transition to oral cephalexin once clinical improvement is demonstrated, typically after 4 days of IV treatment, to complete a total of 5-7 days. 1