What is the appropriate cephalexin (Keflex) dosing regimen for cellulitis in an adult with normal renal function, in children (weight‑based), and in patients with moderate to severe renal impairment?

Cephalexin (Keflex) Dosing for Cellulitis

Standard Adult Dosing (Normal Renal Function)

For typical uncomplicated cellulitis in adults with normal renal function, prescribe cephalexin 500 mg orally every 6 hours (four times daily) for 5 days. 1

• This regimen provides excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, the primary pathogens in 96% of typical cellulitis cases 1
• Treat for exactly 5 days if clinical improvement occurs (resolution of warmth/tenderness, improving erythema, no fever); extend only if symptoms have not improved 1
• High-quality randomized controlled trial evidence confirms 5-day courses are as effective as 10-day courses for uncomplicated cellulitis 1
• Traditional 7–14-day regimens are unnecessary and promote antimicrobial resistance 1

High-Dose Regimen for Severe Cases

• Cephalexin 1000 mg orally every 6 hours may be considered for more severe cellulitis, with preliminary evidence showing fewer treatment failures (3.2% vs 12.9%) compared to standard dosing, though with higher rates of minor gastrointestinal adverse effects 2

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Pediatric Dosing (Weight-Based)

For children with uncomplicated cellulitis, prescribe cephalexin 25–50 mg/kg/day divided into four doses (every 6 hours), with a maximum single dose of 500 mg. 1

Standard Pediatric Regimen

• Mild-to-moderate cellulitis: 25–50 mg/kg/day divided every 6 hours for 5 days 1
• Children may require higher doses per kilogram than adults due to greater body water turnover 3
• Duration is 5 days if clinical improvement is evident; extend only if symptoms persist 1

High-Dose Pediatric Protocol

• For moderate cellulitis managed as outpatients: some institutions use high-dose cephalexin protocols with success rates of 89.7%, potentially reducing hospitalization 4
• This approach requires standardized follow-up within 24–48 hours to verify clinical response 1

Pediatric Hospitalization Criteria

• Admit children <6 months old with moderate-to-severe disease 1
• Admit if systemic inflammatory response syndrome (fever >38°C, tachycardia, tachypnea), hypotension, altered mental status, or concern for necrotizing infection is present 1

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Renal Dosing Adjustments (Moderate-to-Severe Impairment)

Patients with creatinine clearance <30 mL/min require proportional dose reduction based on degree of renal impairment. 3

Specific Adjustments by Creatinine Clearance

• CrCl 30–70 mL/min: Reduce dose or extend dosing interval; consider 500 mg every 8–12 hours instead of every 6 hours 3
• CrCl 10–30 mL/min: 250–500 mg every 12 hours 3
• CrCl <10 mL/min: 250–500 mg every 24 hours 3
• Hemodialysis patients: 250–500 mg after each dialysis session; therapeutic drug monitoring of serum cephalexin concentrations (2 hours and 6 hours post-dose) is recommended to verify adequate exposure while preventing accumulation 1

Monitoring in Renal Impairment

• Determine creatinine clearance or serum creatinine before initiating therapy 3
• For patients with GFR ≈59 mL/min, standard dosing (500 mg every 6 hours) typically requires no adjustment 1

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When MRSA Coverage Is Required (Cephalexin Is Insufficient)

Do not use cephalexin alone when any of the following MRSA risk factors are present:

• Penetrating trauma or injection drug use 1
• Visible purulent drainage or exudate 1
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (fever >38°C, heart rate >90 bpm, respiratory rate >24 breaths/min) 1
• Failure to respond to beta-lactam therapy after 48–72 hours 1

Alternative Regimens When MRSA Coverage Needed

If MRSA risk factors exist, use one of these regimens instead:

• Clindamycin 300–450 mg orally every 6 hours (single-agent coverage for both streptococci and MRSA), but only if local MRSA clindamycin resistance is <10% 1
• Trimethoprim-sulfamethoxazole 1–2 double-strength tablets twice daily PLUS cephalexin 500 mg four times daily (combination required because TMP-SMX lacks reliable streptococcal coverage) 1
• Doxycycline 100 mg orally twice daily PLUS cephalexin 500 mg four times daily (combination mandatory; doxycycline alone misses streptococci) 1

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Special Clinical Scenarios

Diabetic Foot Infections (Broader Coverage Required)

• Diabetic foot cellulitis requires polymicrobial coverage beyond typical cellulitis pathogens 1
• For mild diabetic foot infections: amoxicillin-clavulanate 875/125 mg twice daily is preferred over cephalexin 1
• For moderate infections: consider IV ceftriaxone, ampicillin-sulbactam, or ertapenem 1

Bite-Related Cellulitis

• Amoxicillin-clavulanate 875/125 mg twice daily is preferred over cephalexin for animal or human bite-associated cellulitis because it provides single-agent polymicrobial coverage 1

Penicillin Allergy

• In patients with non-immediate penicillin allergy (e.g., rash), 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
• For true penicillin-allergic patients, use clindamycin 300–450 mg every 6 hours (if local MRSA resistance <10%) 1

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Critical Pitfalls to Avoid

• Do not extend therapy to 7–10 days automatically; extend only if warmth, tenderness, or erythema have not improved after 5 days 1
• Do not add MRSA coverage reflexively for typical non-purulent cellulitis without specific risk factors; MRSA is uncommon even in high-prevalence settings 1
• Do not use doxycycline or TMP-SMX as monotherapy for typical cellulitis; they lack reliable activity against beta-hemolytic streptococci 1
• Do not delay surgical consultation when signs of necrotizing infection (severe pain out of proportion, skin anesthesia, rapid progression, "wooden-hard" tissue) are present 1

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Adjunctive Measures (Essential for Optimal Outcomes)

• 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; treating these eradicates colonization and reduces recurrence 1
• Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and obesity 1

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Monitoring and Reassessment

• Reassess within 24–48 hours to verify clinical response; treatment failure rates of approximately 21% have been reported with some oral regimens 1
• If no improvement after 48–72 hours, consider resistant organisms (MRSA), undrained abscess, deeper infection (necrotizing fasciitis, osteomyelitis), or alternative diagnoses 1