What is the appropriate pediatric dosing of Keflex (cephalexin) for uncomplicated cellulitis, including weight‑based dose (mg/kg per day), dosing every six hours, maximum daily dose, recommended duration, and adjustments for infants younger than two months, renal impairment, severe cephalosporin allergy, and alternative therapy for methicillin‑resistant Staphylococcus aureus (MRSA)?

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Pediatric Cephalexin Dosing for Cellulitis

For uncomplicated cellulitis in children, prescribe cephalexin 25–50 mg/kg/day divided into 4 doses (every 6 hours) for 7 days, with a maximum daily dose of 4 grams. 1

Standard Weight-Based Dosing

  • The Infectious Diseases Society of America recommends cephalexin 25–50 mg/kg/day divided into 3–4 doses for pediatric skin and soft tissue infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus species. 1

  • The traditional dosing interval is every 6 hours (four times daily), though recent pharmacokinetic data support three-times-daily dosing at higher individual doses (up to 45 mg/kg per dose, maximum 1.5 g) for bone and joint infections. 2, 3

  • For cellulitis specifically, the four-times-daily regimen remains the guideline-recommended standard because it maintains consistent bactericidal concentrations against common skin pathogens. 1

Maximum Daily Dose and Duration

  • The maximum daily dose is 4 grams per day, regardless of weight. 1

  • Treatment duration should be 7 days for uncomplicated cellulitis, with clinical improvement expected within 48–72 hours. 1, 4

  • If no improvement occurs by 48–72 hours, reassess for abscess formation requiring drainage, consider MRSA coverage (clindamycin or trimethoprim-sulfamethoxazole), or escalate to parenteral therapy. 1

Adjustments for Infants Younger Than Two Months

  • Cephalexin dosing listed in the IDSA guidelines is not appropriate for neonates; refer to the American Academy of Pediatrics Red Book for neonatal-specific dosing. 1

  • Infants under 3 months with cellulitis should generally be hospitalized for parenteral therapy (cefazolin 50 mg/kg/day divided every 8 hours or nafcillin 100–150 mg/kg/day divided every 6 hours) due to the risk of serious bacterial infection and the need for close monitoring. 1

Renal Impairment Adjustments

  • Cephalexin is renally cleared, and patients with creatinine clearance < 30 mL/min require dose reduction proportional to the degree of renal dysfunction. 5

  • For children with significant renal impairment, consult pediatric nephrology or infectious disease specialists to adjust the dosing interval (e.g., every 8–12 hours instead of every 6 hours) while maintaining therapeutic serum concentrations. 5

Severe Cephalosporin Allergy

  • For children with documented severe (anaphylactic) cephalosporin or penicillin allergy, clindamycin 30–40 mg/kg/day divided into 3–4 doses orally is the preferred alternative for uncomplicated cellulitis. 1, 6

  • Clindamycin provides excellent coverage against both β-hemolytic streptococci and community-acquired MRSA, making it ideal for empiric therapy in penicillin-allergic patients. 1, 6

  • The cross-reactivity risk between penicillins and cephalosporins is approximately 1–3% for non-anaphylactic reactions, so cephalexin may be cautiously used under medical supervision in patients with non-severe penicillin allergy (e.g., rash without angioedema or bronchospasm). 7

Alternative Therapy for MRSA

  • If community-acquired MRSA is suspected (purulent drainage, abscess, failure of β-lactam therapy, or local MRSA prevalence > 10%), switch to clindamycin 30–40 mg/kg/day divided into 3–4 doses orally or trimethoprim-sulfamethoxazole 8–12 mg/kg/day (based on trimethoprim component) divided into 2 doses. 1, 6

  • Clindamycin should only be used empirically when local MRSA clindamycin resistance rates are < 10%; perform D-zone testing on erythromycin-resistant MRSA isolates to detect inducible clindamycin resistance. 1, 6

  • For severe cellulitis with systemic toxicity requiring hospitalization, vancomycin 40–60 mg/kg/day divided every 6–8 hours intravenously is the parenteral drug of choice for MRSA. 1

Clinical Monitoring and Common Pitfalls

  • Expect clinical improvement (reduced erythema, warmth, swelling, and fever) within 48–72 hours; lack of improvement warrants reassessment for abscess, deeper infection, or resistant organisms. 1, 4

  • Underdosing cephalexin (using < 25 mg/kg/day) is a common error that risks treatment failure, especially in regions with intermediate penicillin-resistant S. aureus. 1

  • Failure to consider MRSA in patients with purulent cellulitis, recent antibiotic exposure, or known MRSA colonization is a critical pitfall; these patients require MRSA-active therapy from the outset. 1, 6

  • Do not use cephalexin for cellulitis with systemic signs of toxicity (hypotension, tachycardia, altered mental status) or concern for necrotizing fasciitis; these patients require immediate hospitalization, broad-spectrum IV antibiotics (e.g., vancomycin plus piperacillin-tazobactam), and surgical consultation. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Oxacillin or cefalotin treatment of hospitalized children with cellulitis.

Japanese journal of infectious diseases, 2012

Research

The pharmacology of cephalexin.

Postgraduate medical journal, 1983

Guideline

Clindamycin Dosing Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Treatment Recommendations for Pediatric Pneumonia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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