Is cephalexin (a beta-lactam antibiotic) an effective treatment for a patient with purulent cellulitis, potentially caused by Methicillin-resistant Staphylococcus aureus (MRSA)?

Cephalexin for Purulent Cellulitis: Not Recommended

Cephalexin alone is NOT appropriate for purulent cellulitis when MRSA is suspected—you must add MRSA-active coverage with either trimethoprim-sulfamethoxazole (TMP-SMX) or doxycycline, or switch to clindamycin monotherapy. 1

Why Cephalexin Alone Fails in Purulent Cellulitis

The critical distinction here is purulent versus nonpurulent cellulitis. The Infectious Diseases Society of America explicitly states that purulent cellulitis (characterized by purulent drainage or exudate) requires empirical MRSA coverage, as MRSA is a common pathogen in this presentation 1. Cephalexin, a first-generation cephalosporin, lacks clinically relevant activity against MRSA despite some in vitro data suggesting otherwise 2.

Evidence Against Cephalexin Monotherapy

• Beta-lactam monotherapy succeeds in 96% of typical nonpurulent cellulitis cases, but this success rate does not extend to purulent presentations where MRSA prevalence is substantially higher 1
• Two high-quality randomized controlled trials demonstrated that adding TMP-SMX to cephalexin provided no benefit in nonpurulent cellulitis (85% cure vs 82% cure, risk difference 2.7%, p=0.66), but these studies specifically excluded purulent cases 3, 4
• The 2017 JAMA trial showed clinical cure rates of 83.5% with combination therapy versus 85.5% with cephalexin alone, but again, patients with purulent drainage or abscesses were excluded 4

Correct Treatment Algorithm for Purulent Cellulitis

First-Line Options (Choose One):

Option 1: Combination Therapy

• TMP-SMX 1-2 double-strength tablets twice daily PLUS cephalexin 500 mg four times daily for 5 days 1
• Doxycycline 100 mg twice daily PLUS cephalexin 500 mg four times daily for 5 days 1

Option 2: Monotherapy

• Clindamycin 300-450 mg orally every 6 hours for 5 days (covers both streptococci and MRSA, avoiding need for combination therapy) 1
• Use clindamycin only if local MRSA clindamycin resistance rates are <10% 1

Duration

• Treat for exactly 5 days if clinical improvement occurs 1
• Extend beyond 5 days only if symptoms have not improved within this timeframe 1

Specific Risk Factors Mandating MRSA Coverage

You must add MRSA coverage when any of these are present:

• Purulent drainage or exudate (your scenario) 1
• Penetrating trauma or injection drug use 1
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS) criteria 1
• Failure to respond to beta-lactam therapy after 48-72 hours 5

Critical Pitfalls to Avoid

• Never use TMP-SMX or doxycycline as monotherapy for cellulitis—their activity against beta-hemolytic streptococci is unreliable, and streptococci remain important pathogens even in purulent presentations 1
• Do not assume cephalexin will work for MRSA despite the 2006 study showing 92% cure rates for MRSA infections with cefdinir—this study included incision and drainage procedures that likely contributed to success, and cephalosporins lack accepted clinically relevant in vitro activity against MRSA 2
• Do not reflexively extend treatment to 10-14 days—5 days is sufficient if clinical improvement occurs 1

When to Hospitalize

Admit for IV antibiotics (vancomycin 15-20 mg/kg every 8-12 hours) if:

• SIRS criteria present (fever >38°C, tachycardia >90, hypotension, altered mental status) 1
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing infection (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue) 5
• Failure of outpatient treatment after 24-48 hours 5

Adjunctive Measures

• Elevate the affected extremity to promote gravity drainage of edema 1
• Examine interdigital toe spaces for tinea pedis and treat if present to reduce recurrence 1
• Incision and drainage is mandatory if any abscess is present—antibiotics alone are insufficient 1