Cephalexin (Keflex) Dosing for Skin and Soft Tissue Infections

For uncomplicated skin infections in healthy adults, administer cephalexin 500 mg orally four times daily (every 6 hours) for 7 days. 1

Adult Dosing

Standard oral regimen:

500 mg four times daily (every 6 hours) for uncomplicated skin and soft tissue infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) and streptococci 1
Treatment duration is typically 7 days, depending on clinical response 1
This dosing achieves urinary concentrations of 500–1000 mcg/mL, far exceeding minimum inhibitory concentrations for common pathogens 2

Clinical context:

Cephalexin is the oral agent of choice for methicillin-susceptible strains of staphylococci 1
It provides excellent coverage against S. aureus and Streptococcus pyogenes, the most common skin infection pathogens 1, 3
A recent non-inferiority trial demonstrated that cephalexin 500 mg four times daily was equally effective as intravenous cefazolin for uncomplicated mild-to-moderate skin infections, with 95.8% treatment success at 72 hours 3

Standard oral regimen:

25 mg/kg/day divided into 4 doses (every 6 hours) 1
Children may require higher doses per kilogram than adults due to greater body water turnover 2
Duration is typically 7 days based on clinical response 1

Important consideration:

Doses listed are not appropriate for neonates; refer to specialized neonatal dosing guidelines 1

Dose adjustment required:

Patients with creatinine clearance <30 mL/min require dose reduction proportional to their reduced renal function 2
Cephalexin is 70–100% renally excreted within 6–8 hours, necessitating adjustment in significant renal impairment 2
Establish creatinine clearance or serum creatinine to guide appropriate dose reduction 2

When IV therapy is indicated (severe infections, systemic toxicity, inability to tolerate oral medications):

Cefazolin 1 g every 8 hours IV for adults 1
Cefazolin 33 mg/kg/dose every 8 hours IV for children 1
Nafcillin or oxacillin 1–2 g every 4 hours IV for adults with severe MSSA infections 1
Nafcillin or oxacillin 50 mg/kg/dose every 6 hours IV for children 1

For patients with non-immediate hypersensitivity reactions:

Cephalexin can still be used at standard dosing (500 mg four times daily for adults, 25 mg/kg/day divided into 4 doses for children), as cross-reactivity is low 1

For patients with immediate hypersensitivity (anaphylaxis, urticaria):

Clindamycin 300–450 mg orally three times daily for adults 1
Clindamycin 10–20 mg/kg/day orally divided into 3 doses for children 1
Alternative: Doxycycline 100 mg twice daily for adults (not recommended for children <8 years) 1

Critical caveat for clindamycin:

Use only when local MRSA clindamycin resistance rates are <10% 1
Perform D-zone testing for erythromycin-resistant MRSA to detect inducible clindamycin resistance 1

Underdosing:

Do not prescribe cephalexin 250 mg four times daily for skin infections in adults; the evidence-based dose is 500 mg four times daily 1, 3
Children require weight-based dosing at 25 mg/kg/day, not arbitrary reduced adult doses 1

Inappropriate use:

Cephalexin is ineffective against MRSA; if MRSA is suspected or confirmed, switch to appropriate anti-MRSA therapy 1
Do not use cephalexin for patients with immediate penicillin hypersensitivity reactions 1

Renal failure:

Failure to adjust dosing in patients with creatinine clearance <30 mL/min can lead to drug accumulation and toxicity 2

Duration errors:

Most uncomplicated skin infections require only 7 days of therapy; longer courses (up to 14 days) are reserved for complicated infections with slow clinical response 1