What is the recommended dose of Keflex (cefalexin) for an adult patient with uncomplicated cellulitis and normal renal function?

Keflex Dosing for Cellulitis

For uncomplicated cellulitis in adults with normal renal function, the recommended dose is cephalexin (Keflex) 500 mg orally four times daily (every 6 hours) for 5 days, extending only if clinical improvement has not occurred within this timeframe. 1, 2, 3

Standard Adult Dosing Regimen

• Cephalexin 500 mg orally every 6 hours (four times daily) is the evidence-based dose for uncomplicated cellulitis 2, 3
• The FDA-approved dosage range for adults is 1-4 grams daily in divided doses, with 500 mg every 12 hours specifically approved for skin and skin structure infections 3
• However, the Infectious Diseases Society of America specifically recommends the four-times-daily regimen (500 mg every 6 hours) for optimal streptococcal coverage in cellulitis 1, 2

Treatment Duration

• Treat for exactly 5 days if clinical improvement occurs (resolution of warmth, tenderness, and improving erythema) 1, 2
• Extend treatment beyond 5 days ONLY if the infection has not improved within this initial period 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases, as 5-day courses demonstrate equivalent efficacy 1
• A large randomized trial confirmed that 5 days is as effective as 10 days when clinical improvement occurs by day 5 2

When Cephalexin Monotherapy is Appropriate

Cephalexin alone is successful in 96% of typical cellulitis cases because β-hemolytic streptococci (particularly group A streptococcus) are the predominant pathogens, and MRSA is an uncommon cause 1, 2

• Use cephalexin monotherapy for typical nonpurulent cellulitis without purulent drainage, abscess, or systemic signs 1, 2
• A landmark randomized trial demonstrated that adding trimethoprim-sulfamethoxazole (for MRSA coverage) to cephalexin provided no additional benefit for uncomplicated cellulitis 2, 4
• The clinical cure rate with cephalexin alone was 85.5% in the per-protocol analysis, with no significant difference when MRSA coverage was added 4

When NOT to Use Cephalexin Alone

Do not use cephalexin monotherapy when specific MRSA risk factors are present: 1, 2

• Cellulitis associated with penetrating trauma or injection drug use 1, 2
• Presence of purulent drainage or exudate 1, 2
• Known MRSA colonization or evidence of MRSA infection elsewhere 1
• Systemic inflammatory response syndrome (SIRS) with fever, tachycardia, or hypotension 1

In these scenarios, use clindamycin 300-450 mg four times daily (covers both streptococci and MRSA), or combine trimethoprim-sulfamethoxazole or doxycycline with a beta-lactam 1

Alternative Beta-Lactam Options

If cephalexin is unavailable or not tolerated, alternative oral beta-lactams include: 1, 2

• Penicillin VK 250-500 mg every 6 hours 2
• Amoxicillin 500 mg three times daily 2
• Dicloxacillin 500 mg four times daily 2

Allergy Considerations

• Cephalexin is appropriate for penicillin-allergic patients EXCEPT those with immediate hypersensitivity reactions (anaphylaxis, urticaria) 2
• For patients with true immediate-type penicillin allergy, use clindamycin 300-450 mg four times daily instead 1, 2

Essential Adjunctive Measures

Beyond antibiotics, these interventions hasten improvement: 1, 2

• Elevate the affected extremity above heart level to promote gravitational drainage of edema 1, 2
• Treat predisposing conditions including tinea pedis, venous insufficiency, and chronic edema 1, 2
• Examine interdigital toe spaces for fungal infection and treat if present 1

High-Dose Cephalexin Consideration

• A 2023 pilot trial evaluated cephalexin 1000 mg four times daily versus the standard 500 mg dose 5
• Treatment failure occurred in 12.9% with standard-dose versus 3.2% with high-dose, though high-dose had more minor adverse effects 5
• This remains investigational and is not yet standard practice, but may be considered for severe cases or treatment failures 5

Common Pitfalls to Avoid

• Do not reflexively extend treatment to 7-10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication 1
• Do not add MRSA coverage for typical nonpurulent cellulitis without specific risk factors, as this represents overtreatment and increases resistance 1, 2
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy, as their activity against beta-hemolytic streptococci is unreliable 1