What factors determine the dosage of cephalexin (a cephalosporin antibiotic) for a pediatric patient with cellulitis, particularly in cases of impaired renal function?

Cephalexin Dosing for Pediatric Cellulitis

For pediatric cellulitis, use the standard dose of 25-50 mg/kg/day divided every 6-8 hours, but increase to 75-100 mg/kg/day in severe infections or when treating less susceptible organisms, with dose adjustments required for impaired renal function. 1

Standard Dosing Algorithm

For Uncomplicated Cellulitis (Normal Renal Function)

Base your dosing on infection severity and patient age:

• Mild to moderate cellulitis: 25-50 mg/kg/day divided every 6 hours (four times daily) 1
• Severe cellulitis or less susceptible organisms: Double the standard dose 1
• Alternative twice-daily regimen: For streptococcal infections and skin/skin structure infections, the total daily dose may be divided every 12 hours 1

Recent Evidence for Higher Dosing

• A 2025 study demonstrated that high-dose cephalexin 45 mg/kg/dose (maximum 1.5 g) three times daily achieved 99% cure rates in pediatric bone and joint infections with good tolerability 2
• This reduced-frequency regimen improves adherence while maintaining efficacy 2
• Only 4 patients experienced gastrointestinal symptoms and 13 developed mild neutropenia without complications 2

Renal Function Considerations

Cephalexin is substantially excreted by the kidney, requiring dose adjustment in impaired renal function:

• Monitor renal function before initiating therapy, particularly in patients with known or suspected renal impairment 1
• Reduce dose or extend dosing intervals in patients with decreased creatinine clearance 1
• The risk of toxic reactions increases with impaired renal function 1

Factors Determining Higher vs. Lower Dose

Use HIGHER doses (50-100 mg/kg/day) when:

• Severe infection with extensive erythema, significant swelling, or systemic toxicity 1
• Less susceptible organisms are suspected or confirmed 1
• Treatment failure on standard dosing 3
• Complicated cellulitis requiring more aggressive therapy 1

Use STANDARD doses (25-50 mg/kg/day) when:

• Uncomplicated, nonfacial cellulitis in otherwise healthy children 3
• Mild to moderate infection without systemic symptoms 1
• Normal renal function and no complicating factors 1

Clinical Monitoring Points

Track these parameters to guide dosing decisions:

• Clinical response within 48-72 hours: Decreased erythema, swelling, warmth, and tenderness indicate adequate dosing 4
• Fever resolution: Should occur within 2-3 days; persistent fever suggests inadequate dosing or resistant organisms 4
• Treatment failures: Occurred in 8.9% of patients on standard cephalexin dosing for cellulitis, suggesting some cases may benefit from higher doses 3

Common Pitfalls to Avoid

• Underdosing severe infections: The FDA label explicitly states larger doses may be needed for severe infections 1
• Ignoring renal function: Failure to adjust for impaired renal function increases toxicity risk 1
• Poor adherence with four-times-daily dosing: Consider twice-daily or three-times-daily regimens when appropriate to improve compliance 1, 2
• Premature discontinuation: Complete the full 10-day course even if symptoms improve early 1

Drug Interactions Affecting Dosing

• Metformin co-administration: Increases metformin levels by 24-34%; monitor closely and consider dose adjustment of metformin 1
• Probenecid: Inhibits renal excretion of cephalexin, potentially requiring dose reduction 1

Maximum Dosing Limits

• If daily doses exceed 4 grams are required, switch to parenteral cephalosporins rather than continuing oral cephalexin 1
• For the 333 mg and 750 mg strengths, ensure total daily dose remains within 1-4 grams 1