What is the recommended dosage of Keflex (Cephalexin) for treating cellulitis in adults?

Keflex (Cephalexin) Dosage for Adult Cellulitis

For adults with non-purulent cellulitis, cephalexin 500 mg orally every 6 hours (four times daily) for 5-10 days is the recommended regimen, with 5 days being sufficient for uncomplicated cases that show clinical improvement. 1, 2

Standard Dosing Regimen

• Cephalexin 500 mg orally every 6 hours is the IDSA-recommended dose for typical non-purulent cellulitis 1, 3
• The FDA-approved adult dosage range is 1-4 grams daily in divided doses, with 500 mg every 12 hours specifically indicated for skin and skin structure infections 2
• Treatment duration should be 5 days if clinical improvement occurs, as this is equally effective as 10 days for uncomplicated cellulitis 1
• Extend therapy beyond 5 days only if the infection has not improved within this timeframe 1, 2

When Cephalexin is Appropriate

Cephalexin is the oral agent of choice for cellulitis caused by methicillin-susceptible Staphylococcus aureus and streptococci 1

• Use for non-purulent cellulitis (no purulent drainage, exudate, or abscess) where β-hemolytic streptococci are the primary concern 3, 1
• MRSA is an unusual cause of typical cellulitis—β-lactam monotherapy with cephalexin is appropriate in the absence of abscess, ulcer, or purulent drainage 1
• Suitable for outpatient management in patients without systemic signs of infection 1

When to Modify or Avoid Cephalexin

Do not use cephalexin alone if any of these MRSA risk factors are present: 1

• Purulent drainage or exudate (even without drainable abscess)
• Penetrating trauma
• Evidence of MRSA infection elsewhere on the body
• Nasal colonization with MRSA
• Injection drug use
• Associated abscess or ulcer

For these situations, add MRSA coverage with clindamycin, TMP-SMX, doxycycline, or linezolid 3, 4

Higher Dose Considerations

• For more severe infections or less susceptible organisms, larger doses may be needed 2
• A 2023 pilot trial showed high-dose cephalexin (1000 mg four times daily) had fewer treatment failures (3.2%) compared to standard dose 500 mg (12.9%), though with more minor adverse effects 5
• If daily doses exceeding 4 grams are required, consider parenteral cephalosporins 2

Special Populations and Situations

• Penicillin-allergic patients (except immediate hypersensitivity): cephalexin remains an option 1
• Renal impairment: reduce dosage proportionally when creatinine clearance is <30 mL/min 6
• Morbidly obese patients: standard dosing appears adequate; empiric dose adjustment based solely on BMI may not be necessary 7

Essential Adjunctive Measures

• Elevate the affected extremity to reduce edema 1
• Treat predisposing conditions: tinea pedis (toe web infections), venous insufficiency, lymphedema, eczema 3, 1
• Examine interdigital toe spaces in lower-extremity cellulitis—treating fissuring or maceration reduces recurrence 1

When to Escalate Care

Consider hospitalization or IV therapy if: 1

• Concern for deeper infection (necrotizing fasciitis, abscess)
• Poor adherence to oral therapy anticipated
• Immunocompromised state
• Outpatient treatment failing after 48-72 hours
• Systemic toxicity present

For hospitalized patients with complicated cellulitis, IV cefazolin 0.5-1 gram every 8 hours is appropriate for non-MRSA infections 3

Common Pitfalls to Avoid

• Don't extend treatment unnecessarily—5 days is adequate if clinical improvement has occurred 1
• Don't automatically add MRSA coverage for typical non-purulent cellulitis without specific risk factors 1
• Don't overlook underlying conditions (venous insufficiency, lymphedema, tinea pedis) that predispose to recurrent cellulitis 1
• Don't ignore treatment failure—if no improvement by day 3-5, consider MRSA coverage or alternative diagnosis 3, 1