What is the typical treatment duration with Keflex (cefalexin) for an adult patient with uncomplicated cellulitis?

Treatment Duration for Cellulitis with Keflex (Cephalexin)

Treat uncomplicated cellulitis with cephalexin for exactly 5 days if clinical improvement has occurred, extending only if symptoms have not improved within this timeframe. 1, 2

Standard Dosing and Duration

• Cephalexin 500 mg orally four times daily (every 6 hours) for 5 days is the evidence-based regimen for uncomplicated cellulitis in adults. 1, 2
• The Infectious Diseases Society of America establishes 5 days as the recommended duration, with extension only if infection has not improved within this timeframe. 1
• Multiple randomized controlled trials demonstrate no significant differences in clinical outcomes between 5-6 day courses versus 10-12 day courses. 3, 4
• A landmark RCT showed 98% clinical success with 5 days of therapy compared to 98% with 10 days, confirming shorter courses are equally effective. 4

When to Stop at Day 5

Stop antibiotics after 5 days if the following criteria are met:

• Warmth and tenderness have resolved 3
• Erythema is improving (complete resolution is not required) 3
• Patient is afebrile 3
• No expansion of the affected area 3

When to Extend Beyond 5 Days

Continue treatment and reassess if any of these are present at day 5:

• No reduction in erythema, warmth, or swelling 3
• Persistent fever or systemic signs 3
• Continued expansion of the affected area despite therapy 3
• Underlying conditions such as diabetes, chronic venous insufficiency, or lymphedema that slow response 3

Critical Evidence Supporting 5-Day Duration

• Beta-lactam monotherapy is successful in 96% of patients with typical uncomplicated cellulitis, confirming that shorter courses with appropriate agents are highly effective. 1
• The American College of Physicians recommends 5-6 days of antibiotic therapy for nonpurulent cellulitis, particularly for patients who can self-monitor with close follow-up. 3
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1

Common Pitfall to Avoid

• Do not reflexively extend treatment to 7-10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication—this is a common error that increases antibiotic resistance without improving outcomes. 3
• Prolonged antibiotic exposure beyond 5-7 days increases risk of adverse effects (up to 20% of patients), C. difficile infection, and drives antibiotic resistance. 3

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances. 1
• Examine and treat interdigital tinea pedis, fissuring, scaling, or maceration to eradicate colonization and reduce recurrent infection risk. 1, 3
• Address underlying venous insufficiency, lymphedema, and chronic edema with compression stockings once acute infection resolves. 1, 3

When Cephalexin is Appropriate

• Cephalexin is the standard first-line agent for typical nonpurulent cellulitis without MRSA risk factors. 1, 2
• β-hemolytic streptococci (particularly group A streptococcus) are the predominant pathogens in typical cellulitis, and cephalexin provides excellent coverage. 2
• MRSA is an unusual cause of typical, non-purulent cellulitis—a large randomized trial demonstrated that adding trimethoprim-sulfamethoxazole for MRSA coverage to cephalexin provided no additional benefit. 2

When NOT to Use Cephalexin Alone

Do not use cephalexin monotherapy for cellulitis associated with:

• Penetrating trauma or injection drug use 2
• Purulent drainage or abscess formation 2
• Known MRSA colonization or infection elsewhere 1
• Systemic inflammatory response syndrome (SIRS) 1