For a healthy 36‑year‑old woman with uncomplicated post‑traumatic cellulitis, how many days should cephalexin (Keflex) and trimethoprim‑sulfamethoxazole (Bactrim) be administered?

Treatment Duration for Uncomplicated Post-Traumatic Cellulitis

For a healthy 36-year-old woman with uncomplicated post-traumatic cellulitis, treat with cephalexin 500 mg orally four times daily for exactly 5 days, and do NOT add trimethoprim-sulfamethoxazole (Bactrim) because combination therapy provides no additional benefit over cephalexin alone in pure cellulitis without abscess or purulent drainage. 1, 2, 3

Why Cephalexin Alone for 5 Days

• Beta-lactam monotherapy (cephalexin) achieves 96% clinical success in typical nonpurulent cellulitis because the primary pathogens are beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus 1, 4
• High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis, with no difference in clinical resolution at 14 or 28 days 1, 5
• Traditional 7-14 day regimens are no longer necessary and represent overtreatment 1

Why NOT to Add Bactrim (Trimethoprim-Sulfamethoxazole)

• Two separate randomized controlled trials definitively show that adding trimethoprim-sulfamethoxazole to cephalexin provides no additional benefit in pure cellulitis without abscess, ulcer, or purulent drainage 1, 2, 3
• In the largest trial (500 patients), clinical cure occurred in 83.5% with combination therapy versus 85.5% with cephalexin alone—a difference of -2.0% (95% CI: -9.7% to 5.7%; P=0.50) 2
• A second trial (153 patients) showed 85% cure with combination versus 82% with cephalexin alone (risk difference 2.7%, 95% CI: -9.3% to 15%; P=0.66) 3
• MRSA coverage is unnecessary for typical nonpurulent cellulitis even in high-prevalence settings 1, 4

When You WOULD Add MRSA Coverage (Not This Case)

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

• Penetrating trauma with purulent drainage or exudate (not just trauma alone)
• Injection drug use
• Known MRSA colonization or prior MRSA infection
• Systemic inflammatory response syndrome (fever >38°C, tachycardia, hypotension)
• Failure to respond to beta-lactam after 48-72 hours

Post-traumatic cellulitis alone does NOT mandate MRSA coverage—you need purulent drainage, not just a history of trauma 1

Exact Regimen

• Cephalexin 500 mg orally every 6 hours (four times daily) for 5 days 1
• Extend treatment only if warmth, tenderness, or erythema have not improved after 5 days 1, 5
• Reassess within 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some oral regimens 1

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration and treat if present to reduce recurrence risk 1
• Treat predisposing conditions including venous insufficiency, lymphedema, and chronic edema 1

Common Pitfall to Avoid

Do not reflexively extend antibiotics to 7-10 days based on residual erythema alone—some inflammation persists even after bacterial eradication, and extending treatment based on tradition rather than evidence increases antibiotic resistance without improving outcomes 1, 5