Treatment Duration for Uncomplicated Cellulitis with Keflex (Cephalexin)
Treat uncomplicated cellulitis with Keflex for 5 days if clinical improvement has occurred, extending only if symptoms have not improved within this timeframe. 1, 2
Evidence-Based Rationale
The Infectious Diseases Society of America (IDSA) 2014 guidelines establish 5 days as the recommended duration for antimicrobial therapy in uncomplicated cellulitis, with strong evidence (strong recommendation, high-quality evidence). 1 This represents a significant departure from traditional 7-14 day courses that are no longer necessary for uncomplicated cases. 2
Standard Dosing Regimen
- Cephalexin 500 mg orally every 6 hours (four times daily) is the recommended dose for typical nonpurulent cellulitis in adults with normal renal function. 2
- This regimen provides excellent coverage against the primary pathogens: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus. 2
Clinical Decision Algorithm for Duration
At Day 5, assess the following:
- If warmth and tenderness have resolved, erythema is improving, and patient is afebrile → Stop antibiotics after 5 days. 2
- If no improvement in warmth, tenderness, or erythema → Extend treatment and reassess for complications such as abscess formation, necrotizing infection, or resistant organisms. 1, 2
Supporting Research Evidence
High-quality randomized controlled trials confirm that beta-lactam monotherapy (cephalexin alone) is successful in 96% of uncomplicated cellulitis cases. 2 A landmark JAMA trial demonstrated that adding trimethoprim-sulfamethoxazole to cephalexin provided no additional benefit, with clinical cure rates of 83.5% versus 85.5% for cephalexin alone (difference -2.0%, 95% CI -9.7% to 5.7%). 3 Similarly, a pediatric trial showed no significant difference between cephalexin and clindamycin for uncomplicated skin infections, with 94% versus 97% improvement rates at 48-72 hours. 4
Critical Caveats
- The 5-day duration applies specifically to uncomplicated cellulitis, defined as nonpurulent cellulitis without systemic toxicity, penetrating trauma, purulent drainage, or MRSA risk factors. 2
- Do not reflexively extend treatment to 7-10 days based on residual erythema alone, as some inflammation persists even after bacterial eradication—this is a common error that increases antibiotic resistance without improving outcomes. 2
- MRSA coverage is NOT needed for typical nonpurulent cellulitis, as MRSA is an uncommon cause even in high-prevalence settings, and beta-lactam treatment succeeds in 96% of patients. 2
When to Deviate from 5-Day Treatment
Add MRSA coverage and consider longer duration (7-10 days) if:
- Penetrating trauma or injection drug use is present. 1, 2
- Purulent drainage or exudate is visible. 1, 2
- Evidence of MRSA infection elsewhere or nasal MRSA colonization exists. 1
- Systemic inflammatory response syndrome (SIRS) is present (fever >38°C, tachycardia >90 bpm, hypotension, altered mental status). 1, 2
- Signs of necrotizing fasciitis develop (severe pain out of proportion, skin anesthesia, rapid progression, bullous changes). 2
Essential Adjunctive Measures
- Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances—this hastens improvement and is often neglected. 1, 2
- Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration, as treating these eradicates colonization and reduces recurrent infection risk. 2
- Address predisposing conditions including venous insufficiency, lymphedema, and chronic edema with compression stockings once acute infection resolves. 2