Cephalexin Dosing for Cellulitis
For adults with uncomplicated cellulitis, the standard dose is cephalexin 500 mg orally four times daily (every 6 hours) for 5 days, extending only if clinical improvement has not occurred within this timeframe. 1
Standard Dosing Regimen
Cephalexin 500 mg every 6 hours (four times daily) is the IDSA-recommended standard regimen for typical nonpurulent cellulitis in adults. 1
The treatment duration is 5 days if clinical improvement has occurred, with extension only if symptoms persist—traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1, 2
Beta-lactam monotherapy (including cephalexin) is successful in 96% of cellulitis cases, confirming that MRSA coverage is usually unnecessary. 1, 2
When Cephalexin is Appropriate
Cephalexin is first-line therapy for typical nonpurulent cellulitis without abscess, purulent drainage, or penetrating trauma. 1
This applies to cellulitis presenting as spreading erythema, warmth, and tenderness without any purulent component. 1, 2
The pathogen in typical cellulitis is predominantly beta-hemolytic streptococci or methicillin-sensitive Staphylococcus aureus, both covered by cephalexin. 2
When NOT to Use Cephalexin Alone
Never use cephalexin for cellulitis with purulent drainage, abscess, or penetrating trauma without adding MRSA coverage—this is a common error leading to treatment failure. 1
For purulent cellulitis, use either clindamycin monotherapy (300-450 mg three times daily) OR combination therapy with cephalexin plus trimethoprim-sulfamethoxazole or doxycycline. 1, 3
Cephalexin has no activity against Pasteurella multocida (animal bites) or Eikenella corrodens (human bites)—use amoxicillin-clavulanate instead. 1, 2
First-generation cephalosporins like cephalexin are ineffective for Lyme disease and should not be used when erythema migrans cannot be distinguished from bacterial cellulitis. 4
Evidence Supporting Standard Dosing
A large randomized trial demonstrated that cephalexin plus trimethoprim-sulfamethoxazole was no more efficacious than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage (clinical cure 83.5% vs 85.5%, difference -2.0%, 95% CI -9.7% to 5.7%). 5
This confirms that adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases. 2, 5
A pilot trial comparing high-dose cephalexin (1000 mg four times daily) to standard-dose (500 mg four times daily) showed fewer treatment failures with high-dose (3.2% vs 12.9%), but with more minor adverse effects. 6
Critical Pitfalls to Avoid
Do not reflexively extend treatment beyond 5 days without reassessing clinical response—longer courses are unnecessary for uncomplicated cases and contribute to antibiotic resistance. 1, 2
Do not add MRSA coverage routinely for typical nonpurulent cellulitis—MRSA is an uncommon cause even in high-prevalence settings. 1, 2
Do not use cephalexin as monotherapy for severe cellulitis with systemic toxicity (fever, hypotension, altered mental status)—these patients require hospitalization and IV vancomycin plus piperacillin-tazobactam. 2
Adjunctive Measures That Accelerate Resolution
Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema. 2
Treat predisposing conditions including tinea pedis, toe web abnormalities, venous insufficiency, and lymphedema to reduce recurrence risk. 1, 2
Consider adding ibuprofen 400 mg every 6 hours for 5 days—one study showed this significantly shortened time to regression of inflammation (82.8% showed regression within 1-2 days vs 9.1% with antibiotics alone). 7
Special Populations
For pediatric patients, amoxicillin or cefuroxime axetil are preferred over cephalexin, with dosing based on weight. 4
Pregnant or breastfeeding women should avoid doxycycline but can safely use cephalexin or amoxicillin. 4
For patients with cephalosporin allergy, use clindamycin 300-450 mg orally every 6 hours or penicillin V 250-500 mg four times daily. 2, 3