What is the recommended first‑line oral therapy and dosing of cephalexin (Keflex) for an uncomplicated bacterial skin infection in adults and children?

Cephalexin (Keflex) for Uncomplicated Bacterial Skin Infections

For uncomplicated bacterial skin infections in adults, prescribe cephalexin 500 mg orally every 6 hours (four times daily) for exactly 5 days, extending only if warmth, tenderness, or erythema have not improved. 1, 2, 3

Adult Dosing

• Standard regimen: Cephalexin 500 mg orally every 6 hours (four times daily) for 5 days 1, 2, 3
• Alternative for mild infections: 250 mg every 6 hours may be used, though 500 mg is preferred for reliability 3
• Total daily dose range: 1–4 grams per day divided into doses 3
• Treatment duration: Exactly 5 days if clinical improvement occurs (resolution of warmth/tenderness, improving erythema, no fever); extend only if symptoms persist 1, 2

Pediatric Dosing

• Standard dose: 25–50 mg/kg/day divided into four doses (every 6 hours) 2, 3
• For impetigo: 25 mg/kg/day divided into four doses 2, 3
• Streptococcal pharyngitis or skin infections: May divide total daily dose and administer every 12 hours in children over 1 year 3
• Severe infections: Double the standard dosage 3
• Otitis media: Requires 75–100 mg/kg/day in 4 divided doses 3

Pediatric Weight-Based Dosing Table (125 mg/5 mL suspension, four times daily):

• 10 kg (22 lb): ½ to 1 teaspoon four times daily
• 20 kg (44 lb): 1 to 2 teaspoons four times daily
• 40 kg (88 lb): 2 to 4 teaspoons four times daily 3

When Cephalexin Monotherapy Is Appropriate

• Typical non-purulent cellulitis without drainage, exudate, or abscess 1, 2
• No MRSA risk factors present (no penetrating trauma, injection drug use, purulent drainage, known MRSA colonization, or systemic inflammatory response syndrome) 1, 2
• Beta-lactam monotherapy achieves 96% clinical success in typical cellulitis because the primary pathogens are beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus 1, 2
• Outpatient management is suitable when the patient can self-monitor with close follow-up within 24–48 hours 2

When to Add MRSA Coverage (Do NOT Use Cephalexin Alone)

Add MRSA-active antibiotics when any of these risk factors are present:

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate visible at the infection site 1, 2
• Known MRSA colonization or prior MRSA infection 1, 2
• Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min) 1, 2
• Failure to respond to beta-lactam therapy after 48–72 hours 1, 2

MRSA Coverage Options:

• Clindamycin 300–450 mg orally every 6 hours (single-agent coverage for both streptococci and MRSA, but only if local MRSA clindamycin resistance <10%) 4, 1
• Trimethoprim-sulfamethoxazole 1–2 double-strength tablets twice daily PLUS cephalexin (combination required because TMP-SMX lacks streptococcal coverage) 4, 1
• Doxycycline 100 mg orally twice daily PLUS cephalexin (combination required; doxycycline alone misses streptococci) 4, 1

Renal Dose Adjustment

• Creatinine clearance 30–70 mL/min: No dose adjustment needed for standard 500 mg every 6 hours 2
• Severe renal impairment or hemodialysis: Consult nephrology for individualized dosing and consider therapeutic drug monitoring 1

Intravenous Alternative and Transition Strategy

• Hospitalized patients requiring IV therapy: Cefazolin 1–2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis without MRSA risk factors 1, 2
• Transition to oral: Switch to cephalexin 500 mg every 6 hours once clinical improvement is evident, typically after 4–5 days of IV treatment 1, 2

Reassessment and Treatment Failure

• Mandatory reassessment within 24–48 hours to verify clinical response; oral regimens have reported failure rates up to 21% if no response is seen 1, 2
• If cellulitis worsens after 48–72 hours: Switch to MRSA-active therapy (vancomycin 15–20 mg/kg IV every 8–12 hours or clindamycin) or evaluate for necrotizing infection 1, 2
• Red-flag findings requiring immediate surgical consultation: Severe pain out of proportion to exam, skin anesthesia, rapid progression, "wooden-hard" tissue, gas in soft tissue, bullous changes, or systemic toxicity (hypotension, altered mental status) 1, 2

Adjunctive Non-Antibiotic Measures

• Elevate the affected limb above heart level for at least 30 minutes three times daily to promote edema drainage and accelerate improvement 1, 2
• Inspect interdigital toe spaces for tinea pedis, fissuring, or maceration and treat these conditions to reduce colonization and recurrence 1, 2
• Address underlying conditions: Treat venous insufficiency, lymphedema, chronic edema, obesity, and eczema as part of routine care 1, 2

Critical Pitfalls to Avoid

• Do not automatically extend therapy to 7–10 days based solely on residual erythema; inflammation may persist after bacterial eradication, and high-quality evidence shows 5-day courses are as effective as 10-day courses 1, 2
• Do not add MRSA coverage routinely for typical cellulitis without specific risk factors; MRSA is uncommon in typical non-purulent cellulitis even in high-prevalence settings 1, 2
• Do not use cephalexin for purulent cellulitis or abscesses without adding MRSA coverage, as it lacks MRSA activity 4, 1
• Do not delay surgical consultation when signs of necrotizing infection are present; these infections progress rapidly and require debridement 1, 2
• Cephalexin is ineffective for Lyme disease and should not be used in Lyme-endemic areas without considering alternative agents like cefuroxime or amoxicillin-clavulanate 1

Special Populations

Penicillin Allergy

• Non-immediate penicillin allergy: Cephalexin remains acceptable because cross-reactivity is only 2–4% 1
• Avoid cephalexin in confirmed immediate-type amoxicillin allergy due to identical R1 side chains 1
• True penicillin-allergic patients: Use clindamycin 300–450 mg orally every 6 hours (if local MRSA clindamycin resistance <10%) 1

Pediatric Considerations

• Tetracyclines (doxycycline) contraindicated in children <8 years due to tooth discoloration and bone growth effects 4, 1
• For hospitalized children with complicated cellulitis: Vancomycin 15 mg/kg IV every 6 hours is first-line (A-II evidence) 4, 1
• Clindamycin 10–13 mg/kg IV every 6–8 hours is an alternative for stable children if local resistance <10% 4, 1

Pregnancy

• Cephalexin is generally safe in pregnancy; avoid doxycycline (category D) and fluoroquinolones 4

Evidence Quality

The 5-day treatment duration is supported by high-quality randomized controlled trial evidence showing no difference in outcomes compared with 10-day courses for uncomplicated cellulitis. 1, 2 Traditional 7–14-day regimens are no longer necessary for uncomplicated cases. 1