What is the appropriate dosing regimen of Keflex (cephalexin) for streptococcal pharyngitis or skin/soft‑tissue infection in healthy adults, in children (weight‑based), and in patients with impaired renal function or severe penicillin/cephalosporin allergy?

Keflex (Cephalexin) Dosing for Streptococcal Infections

For streptococcal pharyngitis in adults and adolescents, prescribe cephalexin 500 mg orally twice daily for 10 days; for children, use 20 mg/kg/dose twice daily (maximum 500 mg/dose) for 10 days. 1

Adult Dosing for Streptococcal Pharyngitis

• Standard regimen: 500 mg orally twice daily for 10 days 1
• Alternative dosing: 20 mg/kg/dose twice daily (maximum 500 mg/dose) can be used 1
• The 10-day duration is mandatory to prevent rheumatic fever—do not shorten the course 1

Pediatric Dosing for Streptococcal Pharyngitis

• 20 mg/kg/dose orally twice daily (maximum 500 mg/dose) for 10 days 1
• The liquid suspension formulation facilitates administration in young children 2
• Full 10-day course is essential regardless of symptom resolution 1

Streptococcal Skin and Soft-Tissue Infections

Adults

• 500 mg orally four times daily (every 6 hours) for 7–10 days 3
• The four-times-daily regimen is superior to three-times-daily dosing because cephalexin's short half-life requires every-6-hour administration to maintain therapeutic tissue concentrations 3
• Three-times-daily dosing (500 mg TID) is suboptimal and may lead to treatment failure 3

Children

• For mild-to-moderate infections: 25–50 mg/kg/day divided into four doses (every 6 hours) 1, 3
• For MSSA skin infections: 75–100 mg/kg/day divided into 3–4 doses 3
• Maximum single dose: 500 mg 1

Renal Impairment Dosing

• Patients with creatinine clearance <30 mL/min require dose reduction proportional to renal function 4
• In anephric patients, single doses of 250–500 mg produce high, prolonged serum concentrations with peak levels at 1 hour (though delayed absorption up to 12 hours can occur) 5
• Hemodialysis removes approximately 58% of cephalexin over 6 hours 5
• Adjust dosing frequency based on creatinine clearance or serum creatinine levels 4

Critical Penicillin Allergy Considerations

• Cephalexin is appropriate for patients with non-severe penicillin allergy (e.g., delayed rash) 3, 6
• Absolute contraindication: history of anaphylaxis, angioedema, or urticaria to penicillins 3
• Cross-reactivity risk between penicillins and cephalosporins is 2–4% and relates to allergic reactions, not efficacy 7
• Avoid cephalexin in patients with immediate-type hypersensitivity to penicillin 1, 6

Important Clinical Caveats

When Cephalexin Is NOT Appropriate

• Cephalexin has ZERO activity against MRSA—if MRSA is suspected or confirmed, switch to trimethoprim-sulfamethoxazole, clindamycin, or doxycycline 3
• Poor coverage for Haemophilus influenzae and Moraxella catarrhalis—do not use for sinusitis or respiratory infections where these pathogens are likely 3
• Completely ineffective against Pseudomonas aeruginosa 3
• Not suitable for endocarditis prophylaxis due to 96% resistance rates among viridans group streptococci 3
• Limited anaerobic coverage—unsuitable for deep abscesses or anaerobic infections 3

Resistance Monitoring

• Geographic and temporal variation in GAS resistance to macrolides (azithromycin, clarithromycin) is well-documented, but cephalexin maintains consistent activity against streptococci 1
• Cure rates of 90% or higher continue to be achieved with cephalexin for streptococcal and staphylococcal skin infections after decades of use 2

Dosing Schedule Optimization

• Administer every 6 hours (e.g., 6 AM, 12 PM, 6 PM, 12 AM) to maintain consistent antibiotic levels 3
• For streptococcal pharyngitis, the twice-daily regimen improves compliance while maintaining efficacy 1
• If daily doses exceeding 4 grams are required for severe infections, switch to parenteral cefazolin 1 g IV every 8 hours 3