What is the dosage and treatment duration of Keflex (cephalexin) for Methicillin-Sensitive Staphylococcus Aureus (MSSA) infections?

Cephalexin Dosing for MSSA Infections

For MSSA infections, cephalexin should be dosed at 500 mg orally every 6 hours (or 250 mg every 6 hours for milder infections) in adults, with treatment duration of 7-14 days for most skin and soft tissue infections. 1, 2

Adult Dosing

Standard dosing:

• Mild to moderate skin and soft tissue infections: 250 mg orally every 6 hours 2
• More severe infections or less susceptible organisms: 500 mg orally every 12 hours 1, 2
• Surgical site infections (trunk/extremity): 500 mg orally every 6 hours 1
• Maximum daily dose: 4 grams per day; if higher doses needed, switch to parenteral cephalosporins 2

Treatment duration:

• Uncomplicated skin infections: 7 days 1
• Cystitis: 7-14 days 2
• Osteoarticular infections: Median total treatment duration of 86 days (range 37-337 days), with oral cephalexin comprising approximately 29 days after initial IV therapy 3

Pediatric Dosing

Standard dosing:

• General infections: 25-50 mg/kg/day divided into doses 2
• Skin and soft tissue infections: Total daily dose may be divided every 12 hours for patients >1 year 2
• Severe infections: Dosage may be doubled 2
• Otitis media: 75-100 mg/kg/day in 4 divided doses 2

Optimized dosing based on pharmacokinetic studies:

• Three times daily (TID): 25 mg/kg/dose (maximum 750 mg/dose) achieves pharmacodynamic targets for MSSA with MIC ≤2 mg/L 4
• Twice daily (BID): 22-45 mg/kg/dose for MSSA with MIC 1-2 mg/L; 80 mg/kg/dose for MIC 4 mg/L 5
• For osteoarticular infections: Both TID and four times daily (QID) dosing showed similar clinical cure rates in retrospective data 6

Important Clinical Considerations

When cephalexin is appropriate:

• Only use for confirmed or suspected MSSA infections - cephalexin has no activity against MRSA and should never be used when MRSA is suspected or confirmed 7
• Obtain cultures before starting therapy when possible to confirm methicillin susceptibility 7
• For pyomyositis caused by MSSA: Cefazolin or antistaphylococcal penicillin (nafcillin/oxacillin) is recommended, with cephalexin as an oral step-down option 1

When to avoid cephalexin:

• MRSA infections: Use trimethoprim-sulfamethoxazole, clindamycin, or vancomycin instead 7
• Severe infections with systemic toxicity: Start with IV therapy (cefazolin, nafcillin, or oxacillin) before considering oral step-down 1
• Necrotizing fasciitis or gas gangrene: Requires broad-spectrum IV therapy, not oral cephalexin 1

Common Pitfalls to Avoid

Critical reassessment points:

• Reassess patients at 48-72 hours - if no improvement, obtain cultures, consider imaging (CT/MRI), and switch to alternative antibiotic or broaden coverage for MRSA 8, 7
• Do not assume all staphylococcal infections are methicillin-susceptible without obtaining cultures, especially in areas with high MRSA prevalence 7

Dosing errors:

• Avoid underdosing in severe infections - the FDA label allows up to 4 grams daily, and more severe infections may require 500 mg every 6 hours rather than every 12 hours 2
• For pediatric patients with serious infections (osteoarticular): Ensure at least 3 weeks of effective IV therapy before transitioning to oral cephalexin 3

Storage and preparation:

• Oral suspension must be refrigerated and discarded after 14 days 2
• Shake suspension well before each dose to ensure accurate dosing 2