Can cephalexin be used for an uncomplicated infected leg wound in a patient without β‑lactam allergy or MRSA/Pseudomonas risk factors, and what is the appropriate treatment duration?

Can Cephalexin Be Used for an Uncomplicated Infected Leg Wound?

Yes, cephalexin 500 mg orally every 6 hours for 5 days is the appropriate first-line treatment for an uncomplicated infected leg wound in patients without β-lactam allergy or MRSA/Pseudomonas risk factors. 1

Why Cephalexin Is the Correct Choice

• Beta-lactam monotherapy achieves 96% clinical success in typical nonpurulent cellulitis because the primary pathogens are beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus 1, 2
• Cephalexin provides excellent coverage against both of these organisms and is specifically recommended by IDSA guidelines as a preferred oral beta-lactam for skin and soft tissue infections 1, 2
• MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, making routine MRSA coverage unnecessary and representing overtreatment 1, 2

Dosing and Duration

• Standard dose: cephalexin 500 mg orally every 6 hours (four times daily) 2
• Duration: exactly 5 days if clinical improvement occurs (resolution of warmth/tenderness, improving erythema, no fever); extend only if symptoms have not improved 1, 2
• High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis 2, 3
• Traditional 7-14 day regimens are no longer necessary for uncomplicated cases 2

When NOT to Use Cephalexin Alone

Add MRSA-active antibiotics only when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use
• Purulent drainage or exudate visible at the wound site
• Known MRSA colonization or prior MRSA infection
• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min)
• Failure to respond to beta-lactam therapy after 48-72 hours

MRSA Coverage Regimens (When Risk Factors Present)

If MRSA coverage is needed, use one of these options: 1, 2

• Clindamycin 300-450 mg orally every 6 hours as single-agent therapy (covers both streptococci and MRSA), but only if local MRSA clindamycin resistance is <10%
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin (combination required because TMP-SMX lacks reliable streptococcal coverage)
• Doxycycline 100 mg orally twice daily PLUS cephalexin (combination required because doxycycline lacks reliable streptococcal coverage)

Critical Adjunctive Measures

• Elevate the affected leg above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances 1, 2
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration and treat if present to eradicate colonization and reduce recurrent infection 1, 2
• Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema 1, 2

Mandatory Reassessment

• Re-evaluate within 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens 1, 4
• If no improvement after 48-72 hours of appropriate therapy, consider resistant organisms (MRSA), undrained abscess, deeper infection, or alternative diagnoses 4

Red Flags Requiring Immediate Escalation

Obtain emergent surgical consultation and initiate broad-spectrum IV antibiotics (vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours) if any of these are present: 1, 4

• Severe pain out of proportion to examination findings
• Skin anesthesia
• Rapid progression despite appropriate antibiotics
• Gas in tissue or "wooden-hard" subcutaneous tissues
• Bullous changes or skin necrosis
• Systemic toxicity (hypotension, altered mental status, organ dysfunction)

Common Pitfalls to Avoid

• Do not add MRSA coverage reflexively for typical nonpurulent leg wounds without specific risk factors—this represents overtreatment in ~96% of cases and promotes antimicrobial resistance 1, 2
• Do not use doxycycline or TMP-SMX as monotherapy for typical cellulitis because they lack reliable activity against beta-hemolytic streptococci 1, 2
• Do not automatically extend therapy to 7-10 days based on residual erythema alone; some inflammation persists even after bacterial eradication 2
• Do not continue ineffective antibiotics beyond 48 hours if the infection is progressing—this indicates either resistant organisms or a deeper/different infection than initially recognized 4