What is the recommended oral and intravenous dosing of cephalexin (Keflex) for uncomplicated cellulitis in adults and children, and how should the dose be adjusted for renal impairment?

Cephalexin Dosing for Cellulitis

For uncomplicated cellulitis in adults, prescribe cephalexin 500 mg orally four times daily for 5 days if clinical improvement occurs, extending only if symptoms have not improved within this timeframe. 1

Standard Adult Dosing

• Cephalexin 500 mg orally every 6 hours (four times daily) is the recommended dose for typical nonpurulent cellulitis in adults with normal renal function. 1
• Beta-lactam monotherapy with cephalexin achieves a 96% success rate in typical cellulitis, confirming that MRSA coverage is usually unnecessary. 1
• Treatment duration is exactly 5 days if warmth, tenderness, and erythema are improving; extend only if no clinical improvement has occurred. 1

Pediatric Dosing

• For children with cellulitis, administer cephalexin 25-50 mg/kg/day divided into four doses (every 6 hours). 1
• For impetigo in children, use 25 mg/kg/day in four divided doses. 1

Renal Dose Adjustment

• For patients with creatinine clearance 30-70 mL/min, no dose adjustment is needed for cephalexin 500 mg every 6 hours. 1
• Patients with creatinine clearance less than 30 mL/min require dose reduction proportional to reduced renal function. 2
• Cephalexin is rapidly cleared by the kidneys, with 70-100% of the dose appearing in urine 6-8 hours after administration. 2

When Standard Cephalexin Dosing Is Appropriate

• Use cephalexin monotherapy for nonpurulent cellulitis without drainage, exudate, or systemic signs. 1
• Appropriate when the patient has no MRSA risk factors (no penetrating trauma, injection drug use, purulent drainage, or known MRSA colonization). 1
• Suitable for outpatients who can self-monitor with close follow-up within 24-48 hours. 1

When to Modify or Avoid Cephalexin

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

• Penetrating trauma or injection drug use requires MRSA-active therapy. 1
• Visible purulent drainage or exudate mandates adding MRSA coverage. 1
• For these scenarios, use clindamycin 300-450 mg orally four times daily as monotherapy (covers both streptococci and MRSA), or combine trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin. 1

High-Dose Cephalexin Consideration

• A 2023 pilot trial demonstrated that high-dose cephalexin 1000 mg four times daily had fewer treatment failures (3.2%) compared to standard-dose 500 mg (12.9%), though with a higher proportion of minor adverse effects. 3
• This high-dose regimen may be considered for patients at higher risk of treatment failure, though it is not yet standard practice. 3

Intravenous Alternative

• For hospitalized patients requiring IV therapy, cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis without MRSA risk factors. 1
• Transition to oral cephalexin 500 mg four times daily once clinical improvement is demonstrated, typically after 4-5 days of IV treatment. 1

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema—this hastens clinical improvement and is often neglected. 1
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration, and treat these conditions to eradicate colonization and reduce recurrent infection. 1
• Address underlying venous insufficiency, lymphedema, and chronic edema as part of routine care. 1

Critical Reassessment Points

• Reassess within 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens. 1
• If cellulitis progresses despite 48-72 hours of cephalexin therapy, switch to MRSA-active therapy (vancomycin 15-20 mg/kg IV every 8-12 hours or clindamycin) or evaluate for necrotizing infection. 1
• Warning signs requiring immediate surgical consultation include severe pain out of proportion to examination, skin anesthesia, rapid progression, "wooden-hard" subcutaneous tissues, or systemic toxicity. 1

Common Pitfalls to Avoid

• Do not reflexively extend treatment to 7-10 days based on residual erythema alone—some inflammation persists even after bacterial eradication. 1
• Do not add MRSA coverage routinely for typical cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance. 1
• Do not use first-generation cephalosporins like cephalexin for Lyme disease—they are ineffective and should not be used. 4