In an otherwise healthy adult with a clean or minimally contaminated soft‑tissue wound and no penicillin or cephalosporin allergy, what is the appropriate prophylactic regimen of cephalexin (Keflex) including dose, frequency, and duration?

Cephalexin Prophylaxis for Soft Tissue Wounds

For clean or minimally contaminated soft tissue wounds in healthy adults, cephalexin 500 mg orally four times daily (every 6 hours) for 2 days is the appropriate prophylactic regimen, with no benefit demonstrated for extending treatment beyond this duration. 1

Recommended Dosing Protocol

• Dose: Cephalexin 500 mg orally 1
• Frequency: Every 6 hours (four times daily) 2, 1
• Duration: 2 days maximum 1

The evidence strongly supports limiting prophylaxis duration. A randomized controlled trial specifically examining contaminated traumatic wounds demonstrated that 2-day prophylactic cephalexin therapy is equally effective as 5-day treatment, with infection rates of 8.57% versus 7.14% respectively (no statistical difference, P=0.31). 1 This finding is particularly relevant because the study population had highly contaminated wounds with soil, debris, or feces—representing a more challenging scenario than typical clean wounds. 1

Duration Rationale and Evidence Hierarchy

Antibiotic prophylaxis should not exceed 24 hours for most clean procedures. 3, 2 Current surgical prophylaxis guidelines emphasize that extending prophylaxis beyond 24-48 hours increases antibiotic resistance without improving outcomes. 2 The National Surgical Infection Prevention Project specifically recommends completing antibiotic infusion within 60 minutes before incision and limiting continuation to no more than 24 hours. 3

For traumatic soft tissue wounds specifically:

• Clean wounds require single preoperative dose or 24-hour prophylaxis 2
• Contaminated wounds may warrant up to 2 days based on direct trial evidence 1
• Extension beyond 2 days provides no additional benefit 1

Clinical Decision Algorithm

For clean soft tissue wounds:

• Initiate cephalexin 500 mg orally every 6 hours 2, 1
• Continue for 24 hours only 3, 2
• No extension needed unless specific high-risk factors present 2

For contaminated soft tissue wounds:

• Initiate cephalexin 500 mg orally every 6 hours 1
• Continue for maximum 2 days 1
• Reassess if signs of established infection develop (purulent discharge, expanding erythema, systemic symptoms) 3

When Prophylaxis Transitions to Treatment

Prophylaxis applies only to clean or clean-contaminated wounds without established infection. 3 If the wound demonstrates:

• Purulent drainage 3
• Expanding erythema >5 cm 3
• Systemic signs (fever >38°C, WBC >12,000 or <4,000) 3
• Evidence of deeper tissue involvement 3

Then this represents established infection requiring therapeutic antibiotics (typically 7 days for skin and soft tissue infections), not prophylaxis. 3

Alternative Regimens for Beta-Lactam Allergy

For patients with documented penicillin or cephalosporin allergy:

• Clindamycin 600 mg orally every 8 hours for 24-48 hours 2
• Alternative: Clindamycin 900 mg IV as single dose for surgical prophylaxis 2

Critical Pitfalls to Avoid

Do not routinely extend prophylaxis beyond 24-48 hours. 2 The presence of surgical drains, sutures, or dressings does not justify prolonged antibiotic courses. 2 Extended prophylaxis increases antimicrobial resistance, promotes Clostridioides difficile infection risk, and provides no demonstrated benefit in infection prevention. 2

Do not use third-generation cephalosporins for routine prophylaxis. 4 Despite marketing and availability, agents like ceftriaxone or cefotaxime offer no advantage over first-generation cephalosporins (cephalexin, cefazolin) for soft tissue wound prophylaxis and promote unnecessary resistance. 4, 5

Recognize that incision and drainage alone may be sufficient for abscesses. 6 A randomized trial of skin abscesses (87.8% caused by community-acquired MRSA) showed 90.5% cure with drainage alone versus 84.1% with drainage plus cephalexin—no significant difference. 6 This underscores that for purulent infections, source control is paramount and antibiotics may be unnecessary. 6

Special Considerations

For open fractures or wounds with bone involvement, prophylaxis recommendations differ substantially. 3 These require:

• Broad-spectrum IV antibiotics initiated immediately 3
• Duration of 3 days for type I-II open fractures, 5 days for type III 3
• Single-agent cephalosporin regimens are appropriate for fractures without extensive soft tissue injury 3

Hand wounds and simple lacerations do not require routine prophylaxis unless specific high-risk features are present (heavy contamination, delayed presentation >6-8 hours, immunocompromise). 3