What is the recommended treatment with Keflex (cefalexin) for a patient with right lower leg cellulitis?

Treatment of Right Lower Leg Cellulitis with Keflex (Cephalexin)

Keflex (cephalexin) 500 mg orally four times daily for 5 days is the first-line treatment for uncomplicated right lower leg cellulitis, providing excellent coverage against streptococci and methicillin-sensitive Staphylococcus aureus, the primary pathogens in typical cellulitis. 1, 2

Standard Treatment Regimen

• Cephalexin 500 mg orally every 6 hours (four times daily) is the recommended dose for adults with normal renal function 1, 2
• Beta-lactam monotherapy achieves a 96% success rate in typical uncomplicated cellulitis, confirming that MRSA coverage is unnecessary in most cases 1, 3
• Treatment duration is exactly 5 days if clinical improvement occurs—extend only if symptoms have not improved within this timeframe 1, 2

When Cephalexin Is Appropriate

Cephalexin is the correct choice when the cellulitis is:

• Nonpurulent (no drainage or exudate) 1, 2
• Without penetrating trauma or injection drug use history 1, 2
• No systemic inflammatory response syndrome (SIRS) signs 1, 2
• No evidence of MRSA infection elsewhere or known MRSA colonization 1, 2

The FDA label confirms cephalexin is indicated for skin and skin structure infections caused by Staphylococcus aureus and Streptococcus pyogenes 4

When to Add MRSA Coverage Instead

Do NOT use cephalexin alone if any of these risk factors are present:

• Purulent drainage or exudate visible 1, 2
• Penetrating trauma or injection drug use 1, 2
• Known MRSA colonization or infection elsewhere 1, 2
• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm) 1, 2

For these scenarios, switch to clindamycin 300-450 mg orally four times daily (covers both streptococci and MRSA), or combine trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin 1, 2, 5

Critical Evidence Supporting This Approach

• A landmark randomized controlled trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit for cellulitis without abscess, ulcer, or purulent drainage—the cure rate was 85% with combination therapy versus 82% with cephalexin alone (not statistically significant) 6
• This confirms the IDSA guideline that MRSA coverage is unnecessary for typical nonpurulent cellulitis 1, 6

Monitoring and Follow-Up

Assess for clinical improvement within 48-72 hours:

• Reduction in erythema, warmth, and swelling 2
• Decreased pain and tenderness 2
• Resolution of fever if present 2

If no improvement by day 5: Reassess for MRSA risk factors, necrotizing infection, or misdiagnosis—consider switching to vancomycin or linezolid if MRSA is suspected 1

Essential Adjunctive Measures

• Elevate the affected leg above heart level for at least 30 minutes three times daily—this promotes gravity drainage of edema and hastens improvement 1, 2
• Examine interdigital toe spaces for tinea pedis (fissuring, scaling, maceration)—treating this eradicates colonization and reduces recurrence risk 1, 2
• Address underlying venous insufficiency, lymphedema, and chronic edema with compression stockings once acute infection resolves 1, 2

Common Pitfalls to Avoid

• Do not reflexively extend treatment to 7-10 days based on residual erythema alone—some inflammation persists even after bacterial eradication 1
• Do not add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection 1

Alternative Dosing Consideration

• A pilot randomized controlled trial suggested that high-dose cephalexin 1000 mg four times daily may reduce treatment failure rates (3.2% vs 12.9% with standard dose), though with higher minor adverse effects 7
• This higher dose could be considered for patients at higher risk of treatment failure, though standard 500 mg dosing remains guideline-recommended 1, 2

When to Hospitalize

Admit for IV antibiotics if any of the following are present:

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1, 2
• Severe immunocompromise or neutropenia 1, 2
• Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissues) 1
• Failed outpatient oral therapy 2

For hospitalized patients, cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis without MRSA risk factors 1