What is the recommended treatment with Keflex (cephalexin) for an adult patient with a mild to moderate skin infection and no known allergies to cephalexin?

Cephalexin (Keflex) for Skin Infections in Adults

Standard Treatment Regimen

For mild to moderate uncomplicated skin infections in adults without MRSA risk factors, cephalexin 500 mg orally every 6 hours (four times daily) for 5 days is the recommended first-line treatment, extending only if clinical improvement has not occurred within this timeframe. 1, 2

When Cephalexin Is Appropriate

Cephalexin provides excellent coverage against the primary pathogens causing typical nonpurulent cellulitis:

• Beta-hemolytic streptococci (especially Streptococcus pyogenes) 2, 3
• Methicillin-sensitive Staphylococcus aureus (MSSA) 2, 3

Use cephalexin for:

• Nonpurulent cellulitis without drainage or exudate 2
• Impetigo (250 mg four times daily in adults) 1
• Uncomplicated skin and soft tissue infections 4

Beta-lactam monotherapy succeeds in 96% of typical cellulitis cases, confirming that MRSA coverage is usually unnecessary. 2

When NOT to Use Cephalexin Alone

Do not use cephalexin monotherapy when MRSA risk factors are present: 2

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Known MRSA colonization or prior MRSA infection 2, 3
• Systemic inflammatory response syndrome (SIRS) 2
• Failure to improve on beta-lactam therapy within 48-72 hours 3

For these scenarios, switch to:

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA) 1, 2, OR
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam 1, 2, OR
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1, 2

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs—warmth and tenderness resolved, erythema improving, patient afebrile. 2 Extension to 7-10 days is only warranted if symptoms have not improved within this timeframe. 1, 2 Traditional 10-14 day courses based on residual erythema alone represent overtreatment and increase antibiotic resistance without improving outcomes. 2

Penicillin Allergy Considerations

Cephalexin can be used in patients with penicillin allergy except those with immediate hypersensitivity reactions. 2, 5 Cross-reactivity between penicillins and cephalosporins is only 2-4%, primarily based on R1 side chain similarity rather than the beta-lactam ring. 1, 2 However, cephalexin shares identical R1 side chains with amoxicillin, so avoid cephalexin in patients with confirmed immediate-type amoxicillin allergy. 2

Renal Dosing

For patients with GFR ≥59 mL/min, use the standard dose of cephalexin 500 mg every 6 hours with no adjustment needed. 2 In markedly impaired renal function, administer with caution and consider lower doses. 5

Critical Warnings

• Discontinue immediately if allergic reaction occurs and treat with epinephrine, antihistamines, or corticosteroids as needed 5
• Cephalexin has NO activity against MRSA—if MRSA is suspected or confirmed, alternative agents must be used 2, 3, 4
• Monitor for Clostridium difficile-associated diarrhea (CDAD), which can occur up to 2 months after antibiotic completion 5
• Obtain cultures when possible before starting antibiotics to guide therapy, especially in treatment failures 3

Adjunctive Measures

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

When to Hospitalize

Admit patients with: 2

• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm)
• Hypotension or hemodynamic instability
• Altered mental status or confusion
• Severe immunocompromise or neutropenia
• Concern for necrotizing infection (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes)

For hospitalized patients requiring IV therapy, use cefazolin 1-2 g IV every 8 hours as the preferred IV beta-lactam for uncomplicated cellulitis. 2