What is the recommended treatment for an adult patient with cellulitis, considering cephalexin (a cephalosporin antibiotic) as a potential option?

Cephalexin for Cellulitis

Cephalexin 500 mg orally every 6 hours for 5 days is the preferred first-line treatment for typical uncomplicated cellulitis in adults, with extension beyond 5 days only if clinical improvement has not occurred. 1, 2

Standard Dosing and Duration

Cephalexin provides excellent coverage against the primary pathogens in cellulitis: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus. 1, 2 The FDA-approved dosing for skin and skin structure infections is 250 mg every 6 hours, but 500 mg every 6 hours is the guideline-recommended dose for cellulitis. 1, 2

Beta-lactam monotherapy with cephalexin succeeds in 96% of typical cellulitis cases, confirming that MRSA coverage is usually unnecessary. 1 The Infectious Diseases Society of America explicitly recommends 5 days of treatment if clinical improvement occurs, based on high-quality randomized controlled trial evidence showing 5-day courses are as effective as 10-day courses. 1

When Cephalexin Alone Is Appropriate

Use cephalexin monotherapy for typical nonpurulent cellulitis without the following risk factors: 1

• No penetrating trauma or injection drug use
• No purulent drainage or exudate visible
• No evidence of MRSA infection elsewhere or known MRSA colonization
• No systemic inflammatory response syndrome (fever >38°C, tachycardia >90, hypotension, altered mental status)

MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, and routine MRSA coverage represents overtreatment. 1, 3

When to Add MRSA Coverage Instead

If any of the following MRSA risk factors are present, do NOT use cephalexin alone—add MRSA-active therapy: 1

• Purulent drainage or exudate → Use clindamycin 300-450 mg every 6 hours alone (covers both streptococci and MRSA), OR trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin 1
• Penetrating trauma or injection drug use → Same MRSA-active regimens 1
• Systemic toxicity (SIRS criteria) → Hospitalize and use IV vancomycin 15-20 mg/kg every 8-12 hours 1
• Failure to respond to cephalexin after 48-72 hours → Add trimethoprim-sulfamethoxazole or switch to clindamycin 1, 4

In a high MRSA-prevalence area, antibiotics without CA-MRSA activity had 4.22 times higher odds of treatment failure (95% CI 2.25-7.92). 4 However, this applies primarily to purulent cellulitis, not typical nonpurulent cellulitis where streptococci predominate. 3

Pediatric Dosing

For children, the recommended dose is 25-50 mg/kg/day divided every 6 hours (or every 12 hours for streptococcal pharyngitis and skin infections). 2 For severe infections, the dosage may be doubled. 2

Renal Dosing

For patients with GFR 59 mL/min, no dose adjustment is needed for cephalexin 500 mg every 6 hours. 1 Standard dosing applies for most patients with mild-to-moderate renal impairment. 1

Essential Adjunctive Measures

Beyond antibiotics, these interventions hasten recovery: 1

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat with antifungals to eradicate colonization 1
• Address underlying venous insufficiency, lymphedema, or chronic edema with compression stockings once acute infection resolves 1

High-Dose Cephalexin: Emerging Evidence

A 2023 pilot randomized controlled trial compared cephalexin 1000 mg four times daily versus 500 mg four times daily for 7 days in ED patients with cellulitis. 5 Treatment failure occurred in 12.9% of the standard-dose arm versus 3.2% in the high-dose arm, though minor adverse events were more common with high-dose therapy. 5 This preliminary evidence suggests high-dose cephalexin may reduce treatment failure, but current guidelines still recommend standard 500 mg dosing. 1, 5

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this increases antibiotic resistance without improving outcomes 1, 3
• Do not extend treatment to 10-14 days based on residual erythema alone—some inflammation persists even after bacterial eradication 1
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy—their activity against beta-hemolytic streptococci is unreliable 1
• Do not delay reassessment beyond 48-72 hours—treatment failure rates of 21% have been reported with some regimens, requiring prompt adjustment 1

When to Hospitalize

Admit patients with any of the following: 1

• SIRS criteria (fever, hypotension, tachycardia, altered mental status)
• Severe immunocompromise or neutropenia
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissues)
• Failure of outpatient therapy after 24-48 hours

For hospitalized patients requiring IV therapy, cefazolin 1-2 g IV every 8 hours is the preferred beta-lactam, not oral cephalexin. 1