Cephalexin Dosing for Cellulitis
For an otherwise healthy adult with uncomplicated cellulitis, prescribe cephalexin 500 mg orally every 6 hours (four times daily) for 5 days. 1, 2, 3
Standard Dosing Regimen
- Cephalexin 500 mg orally every 6 hours is the recommended dose for typical non-purulent cellulitis in adults with normal renal function 1, 2
- Treatment duration is exactly 5 days if clinical improvement occurs (reduced warmth, tenderness, erythema, and absence of fever); extend only if symptoms have not improved within this timeframe 1, 2
- High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis, making traditional 7–14-day regimens unnecessary 1
Why This Dose Works
- Cephalexin provides excellent coverage against the primary pathogens: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, which cause approximately 96% of typical cellulitis cases 1, 2
- Beta-lactam monotherapy achieves 96% clinical success in typical non-purulent cellulitis, confirming that MRSA coverage is usually unnecessary 1
- The FDA-approved adult dosage for skin and skin structure infections ranges from 1 to 4 grams daily in divided doses, with 500 mg every 12 hours as an alternative for uncomplicated cases 3
Alternative Dosing Options
- Cephalexin 500 mg every 12 hours (twice daily) is FDA-approved for uncomplicated skin infections and may improve compliance, though four-times-daily dosing is more commonly recommended in guidelines 3
- Higher doses (1000 mg four times daily) showed fewer treatment failures in a pilot trial but with more minor adverse effects; this is not yet standard practice 4
When MRSA Coverage Is NOT Needed
- Do not routinely add MRSA-active antibiotics for typical non-purulent cellulitis, as MRSA is an uncommon cause even in high-prevalence settings 1, 2
- Adding trimethoprim-sulfamethoxazole to cephalexin provides no additional benefit in pure cellulitis without abscess, ulcer, or purulent drainage 1
When to Add MRSA Coverage Instead
Add MRSA-active therapy (such as clindamycin or TMP-SMX plus a beta-lactam) only when any of these risk factors are present:
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 1
- Known MRSA colonization or prior MRSA infection 1
- Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm) 1
- Failure to respond to beta-lactam therapy after 48–72 hours 1
Critical Pitfalls to Avoid
- Do not extend therapy to 7–10 days automatically; extend only if warmth, tenderness, or erythema have not improved after 5 days 1, 2
- Do not use cephalexin as monotherapy for bite-related cellulitis; use amoxicillin-clavulanate 875/125 mg twice daily instead for polymicrobial coverage 1
- Avoid cephalexin in patients with immediate hypersensitivity reactions (anaphylaxis, urticaria) to penicillins, though it is appropriate for non-immediate penicillin allergies 2
- One retrospective study found a 40% failure rate with cephalexin versus 20% for comparator antibiotics, possibly related to concurrent acid suppression therapy; consider this in patients on proton pump inhibitors 5
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
- Treat predisposing conditions including tinea pedis, venous insufficiency, lymphedema, and chronic edema to reduce recurrence risk 1, 2
- Reassess within 24–48 hours to verify clinical response, as treatment failure rates of approximately 21% have been reported with some oral regimens 1