Treatment Duration for Keflex (Cephalexin) in Skin Infections
For uncomplicated skin infections, treat with Keflex for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1
Evidence-Based Duration Guidelines
The Infectious Diseases Society of America (IDSA) establishes 5 days as the recommended duration for most bacterial skin and soft tissue infections, with extension to 7-14 days only when clinical response is inadequate 1. This represents a significant departure from traditional 10-14 day courses that were based on convention rather than evidence.
Standard 5-Day Course
- The IDSA 2014 guidelines explicitly state that treatment duration should be 7 days, depending on clinical response for non-purulent skin and soft tissue infections 1
- Multiple high-quality randomized controlled trials demonstrate that 5-6 day courses achieve equivalent outcomes to 10-12 day courses for uncomplicated cellulitis 1
- Clinical improvement by day 5 is the key indicator that treatment can be stopped—this means reduction in erythema, warmth, and swelling 2
When to Extend Beyond 5 Days
Extend treatment to 7-14 days only if any of the following are present at day 5 assessment 1, 3:
- No reduction in erythema, warmth, or swelling
- Persistent fever or systemic signs of infection
- Continued expansion of the affected area despite therapy
- Underlying conditions such as diabetes, chronic venous insufficiency, or lymphedema that slow response
Specific Keflex Dosing Regimens
Adults
- Cephalexin 500 mg orally every 6 hours (four times daily) for typical nonpurulent skin infections 4
- For mild infections, 250 mg every 6 hours may be appropriate 4
- Treatment duration: 5 days if improved; 7-10 days if not improved 1, 2
Pediatric Dosing
- 25 mg/kg/day divided into four doses for children 5
- Studies demonstrate 10-day courses in pediatric populations, though shorter courses are increasingly supported 5
Clinical Algorithm for Duration Decision
Day 0-5: Initial Treatment Phase
- Start Keflex at appropriate dose for infection severity
- Reassess at 48-72 hours to verify response 4
Day 5 Assessment: Critical Decision Point
- If improved (reduced warmth, erythema, swelling; patient afebrile): STOP antibiotics 1, 2
- If not improved: Extend to 7-10 days and reassess for complications 1
- If worsening: Consider treatment failure—evaluate for MRSA, abscess, or necrotizing infection 4
Important Caveats and Pitfalls
Common Errors to Avoid
- Do not reflexively extend to 10-14 days based on residual erythema alone—some inflammation persists even after bacterial eradication 2
- Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or deeper infection 4
- Mandatory reassessment in 24-48 hours is essential, as treatment failure rates of 21% have been reported with some oral regimens 4
When Keflex is NOT Appropriate
Keflex should not be used as monotherapy in the following scenarios 4:
- Purulent drainage or exudate present—requires MRSA coverage
- Penetrating trauma or injection drug use—high MRSA risk
- Systemic inflammatory response syndrome (SIRS)—requires broader coverage
- Known MRSA colonization or infection elsewhere
Comparative Evidence
Research demonstrates that cephalexin 500 mg four times daily for 10 days achieves 93-98% clinical cure rates for uncomplicated skin infections 6, 7. However, twice-daily dosing regimens show equivalent efficacy and may enhance compliance 8. The key distinction is that modern evidence supports stopping at 5 days rather than completing the full 10-day course if clinical improvement occurs 1.
Resistance Prevention
- The maximum duration should not exceed 14 days to prevent resistance development 3
- Prolonged antibiotic exposure increases risk of adverse effects (up to 20% of patients), C. difficile infection, and antibiotic resistance 2