What is the appropriate cephalexin (Keflex) dosing for a 16‑year‑old adolescent weighing 140 lb (≈63 kg) with an uncomplicated skin infection?

Cephalexin Dosing for Skin Infection in a 16-Year-Old, 140 lb Patient

For a 16-year-old weighing 140 lb (63.5 kg) with an uncomplicated skin infection, prescribe cephalexin 500 mg orally four times daily for 7–10 days, which falls within the FDA-approved adult dosing range of 1–4 g per day in divided doses. 1

Weight-Based Dosing Calculation

• The patient weighs approximately 63.5 kg (140 lb ÷ 2.2). 1
• The FDA label specifies that pediatric patients should receive 25–50 mg/kg/day in divided doses for skin and skin structure infections. 1
• At 63.5 kg, the calculated pediatric dose would be 1,588–3,175 mg per day (25–50 mg/kg × 63.5 kg). 1
• However, for adolescents at or near adult weight, adult dosing regimens are appropriate: the standard adult dose for skin infections is 500 mg every 6 hours (four times daily), totaling 2,000 mg per day. 1

Dosing Regimen Options

• Standard regimen: Cephalexin 500 mg orally four times daily (every 6 hours) for 7–10 days is the FDA-approved adult dose for skin and skin structure infections. 1
• Alternative twice-daily regimen: For uncomplicated skin infections, 500 mg every 12 hours may be administered, though the four-times-daily regimen provides more consistent drug levels. 1
• The IDSA guidelines recommend 25–50 mg/kg/day divided into 3–4 doses for pediatric cellulitis, which translates to approximately 1,588–3,175 mg per day for this patient's weight; the 500 mg four times daily regimen (2,000 mg/day) falls appropriately within this range. 2

Treatment Duration and Monitoring

• Continue therapy for 7–10 days depending on clinical response; most uncomplicated skin infections resolve within this timeframe. 2, 1
• Clinical improvement should be evident within 48–72 hours, including reduced erythema, warmth, and swelling. 2, 3
• If no improvement occurs by 48–72 hours, consider MRSA coverage (the patient may require clindamycin, trimethoprim-sulfamethoxazole, or doxycycline) or alternative diagnoses. 2, 3

When Cephalexin Is Appropriate

• Cephalexin is the first-line oral agent for non-purulent cellulitis caused by β-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus (MSSA). 2, 3
• It is appropriate in regions with low community-acquired MRSA prevalence and in patients without systemic toxicity or signs of MRSA infection (such as purulent drainage, abscess formation, or recent MRSA history). 2, 3
• Do not use cephalexin for purulent cellulitis or abscesses; these require empirical MRSA coverage with clindamycin (300–450 mg orally four times daily) or trimethoprim-sulfamethoxazole (1–2 double-strength tablets twice daily). 2

Clinical Evidence Supporting Cephalexin

• A 2018 randomized controlled trial demonstrated that cephalexin 500 mg four times daily was non-inferior to intravenous cefazolin plus probenecid for uncomplicated mild-to-moderate skin and soft tissue infections, with failure rates of 4.2% versus 6.1% at 72 hours. 4
• A 2006 study comparing cefdinir to cephalexin showed clinical cure rates of 89% for both agents in adolescents and adults with uncomplicated skin infections, confirming cephalexin's efficacy. 5
• Notably, both studies found that cephalosporins achieved high cure rates even in MRSA-infected patients (90–92%), likely due to incision and drainage or spontaneous drainage contributing to clinical response; however, cephalosporins lack reliable in vitro activity against MRSA and should not be relied upon for documented MRSA infections. 5

Common Pitfalls and Caveats

• Underdosing is a frequent error: prescribing 250 mg four times daily (1,000 mg/day) is inadequate for this patient's weight and may lead to treatment failure. 1
• Cephalexin has no activity against MRSA; if purulent drainage, abscess, or MRSA risk factors are present, empirical MRSA coverage is mandatory. 2, 3
• Do not use cephalexin for erythema migrans (Lyme disease), as first-generation cephalosporins are ineffective against Borrelia burgdorferi. 3
• For penicillin-allergic patients with non-anaphylactic reactions, cephalexin may be used cautiously (cross-reactivity risk is 1–3%); for severe IgE-mediated allergy, use clindamycin or a fluoroquinolone instead. 2, 3

Practical Administration

• Administer with or without food; taking with food may reduce gastrointestinal upset. 1
• Refrigerate oral suspension after reconstitution and discard after 14 days. 1
• Complete the full 7–10 day course even if symptoms improve earlier to prevent relapse and reduce resistance. 2, 3