What is the recommended dosing of cephalexin (Keflex) for uncomplicated cellulitis in adults and children, including treatment duration, renal dose adjustments, and alternative oral agents for patients allergic to penicillins or cephalosporins?

Cephalexin Dosing for Cellulitis

Standard Adult Dosing Regimen

For uncomplicated cellulitis in adults, cephalexin 500 mg orally every 6 hours (four times daily) for 5 days is the recommended regimen, extending treatment only if warmth, tenderness, or erythema have not improved by day 5. 1, 2

• The 5-day duration is supported by high-quality randomized controlled trial evidence showing equivalent efficacy to 10-day courses when clinical improvement occurs 1, 2
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1
• Cephalexin provides excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, the primary pathogens in typical cellulitis 1, 2

Pediatric Dosing

For children with uncomplicated cellulitis, cephalexin 25-50 mg/kg/day divided every 6 hours (four times daily) is the standard regimen. 1

• Alternative twice-daily dosing at 22-45 mg/kg per dose may be considered for MSSA infections with MIC ≤2 mg/L to improve adherence 3
• Thrice-daily dosing at 15-25 mg/kg per dose is another option for reducing medication burden while maintaining efficacy 3
• These less frequent dosing regimens should be prospectively evaluated before routine clinical use 3

Renal Dose Adjustments

For patients with GFR ≥59 mL/min, no dose adjustment is required; use the standard 500 mg every 6 hours regimen. 1

• For patients with end-stage renal disease on hemodialysis, therapeutic drug monitoring of serum cephalexin concentrations is recommended, with levels obtained 2 and 6 hours post-dose to guide adjustments 1

When Cephalexin Is Appropriate vs. When It's Not

Appropriate Use:

• Typical nonpurulent cellulitis without drainage or exudate 1, 2
• Patients without MRSA risk factors 1, 2
• Outpatients who can self-monitor with close follow-up 1
• Penicillin-allergic patients EXCEPT those with immediate hypersensitivity reactions (anaphylaxis, urticaria) 1, 2

Inappropriate Use—Add MRSA Coverage Instead:

• Cellulitis with penetrating trauma or injection drug use 1, 2
• Visible purulent drainage or exudate 1, 2
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (SIRS) present 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

Critical Evidence: MRSA Coverage Is Usually Unnecessary

Beta-lactam monotherapy with cephalexin achieves 96% clinical success in typical nonpurulent cellulitis, confirming that MRSA coverage is unnecessary in most cases. 1, 4, 5

• A landmark randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole (for MRSA coverage) to cephalexin provided no additional benefit for uncomplicated cellulitis 2, 4, 5
• MRSA is an uncommon cause of typical nonpurulent cellulitis even in high-prevalence settings 1, 2

Alternative Oral Agents for Penicillin/Cephalosporin Allergy

For patients with true penicillin and cephalosporin allergies, clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA, but use only if local MRSA clindamycin resistance rates are <10%. 1, 2

Other Alternatives:

• Dicloxacillin 250-500 mg every 6 hours 1, 2, 6
• Penicillin VK 250-500 mg every 6 hours 1, 2
• Amoxicillin 500 mg three times daily 1, 2
• Fluoroquinolones (levofloxacin 500 mg daily) reserved for beta-lactam allergies only 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—this represents overtreatment in 96% of typical cellulitis cases 1, 2, 4, 5
• Avoid cephalexin in patients with immediate-type amoxicillin allergy—cephalexin shares identical R1 side chains with amoxicillin 1
• Concurrent acid suppressive therapy may reduce cephalexin efficacy—one study showed 40% failure rate with cephalexin versus 20% with comparators, possibly related to acid suppression 7

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat to reduce recurrence risk 1
• Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema 1, 2