Is Keflex (cephalexin) effective for treating uncomplicated cellulitis?

Keflex (Cephalexin) for Uncomplicated Cellulitis

Cephalexin (Keflex) is effective as a first-line treatment for uncomplicated cellulitis, with a recommended dosage of 500 mg orally four times daily for 5-7 days. 1, 2

Efficacy and Rationale

• Cephalexin is FDA-approved for skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes, which are the primary pathogens in uncomplicated cellulitis 2
• The American College of Physicians and Infectious Diseases Society of America recommend cephalexin as a first-line therapy for nonpurulent cellulitis 1
• Nonpurulent cellulitis is primarily caused by beta-hemolytic streptococci, for which beta-lactams like cephalexin provide appropriate coverage 3, 1
• A 5-6 day course of antibiotics active against streptococci is recommended for patients with nonpurulent cellulitis who can self-monitor and have close follow-up 3

Dosing and Duration

• Standard dosing for adults is cephalexin 500 mg orally four times daily 3, 1
• Recent evidence suggests that a 5-day course is as effective as a 10-day course if clinical improvement occurs within the first 5 days 3, 1
• A recent pilot study is investigating whether high-dose cephalexin (1000 mg four times daily) may be more effective than standard dosing, with preliminary results showing fewer treatment failures but more minor adverse effects 4

MRSA Considerations

• MRSA is an unusual cause of typical nonpurulent cellulitis 1, 5
• Standard beta-lactam therapy with cephalexin is successful in approximately 96% of typical cellulitis cases 1
• MRSA coverage should be considered only in specific situations:
  • Cellulitis associated with penetrating trauma 3, 1
  • Evidence of MRSA infection elsewhere 1
  • Nasal colonization with MRSA 1
  • Injection drug use 1
  • Systemic inflammatory response syndrome 1
  • Purulent drainage 1, 5

Evidence from Clinical Trials

• A randomized controlled trial comparing cephalexin alone versus cephalexin plus trimethoprim-sulfamethoxazole (for MRSA coverage) found no significant difference in clinical cure rates for uncomplicated cellulitis (82% vs. 85% in the per-protocol analysis) 6
• Another randomized trial similarly found no benefit to adding trimethoprim-sulfamethoxazole to cephalexin for cellulitis treatment (82% cure with cephalexin alone vs. 85% with combination therapy) 7
• These findings support the use of cephalexin alone for typical nonpurulent cellulitis 6, 7

Adjunctive Measures

• Elevation of the affected area is recommended to promote drainage of edema and inflammatory substances 1
• Treatment of underlying conditions that may predispose to infection (e.g., tinea pedis, venous eczema, lymphedema) is important 1
• For patients with purulent collections, incision and drainage is the primary treatment, with antibiotics as adjunctive therapy 3, 1

Clinical Pearls and Pitfalls

• Inflammation may worsen after initiating therapy due to pathogen destruction releasing enzymes that increase local inflammation 1
• It is essential to distinguish cellulitis from purulent collections, as the latter requires drainage rather than antibiotics alone 1
• If no improvement is seen after 48-72 hours of cephalexin therapy, consider alternative diagnoses or the need for MRSA coverage 3, 1
• For patients with penicillin allergies, clindamycin is an appropriate alternative (300-450 mg orally three times daily) 3, 1