Cephalexin (Keflex) for Toxic Shock Syndrome Prophylaxis
Critical Clarification: TSS Prophylaxis vs. Treatment
Cephalexin is NOT recommended for toxic shock syndrome (TSS) prophylaxis or treatment. TSS requires aggressive supportive care, surgical drainage/debridement of the staphylococcal source, and anti-staphylococcal antibiotics that suppress toxin production—cephalexin does not fulfill these requirements 1.
Why Cephalexin Is Inappropriate for TSS
TSS is caused by Staphylococcus aureus exotoxins, not by bacterial proliferation alone, requiring antibiotics that inhibit protein synthesis (and thus toxin production) such as clindamycin 1.
Cephalexin is a beta-lactam antibiotic that works by disrupting cell wall synthesis; it does NOT suppress toxin production and may paradoxically increase toxin release by causing bacterial lysis 2.
Treatment of TSS mandates drainage and debridement of the infection source (e.g., nasal packing removal, wound debridement) plus supportive care for multi-system organ failure, with antibiotics playing a secondary role 1.
Appropriate Anti-Staphylococcal Agents for TSS
For Methicillin-Susceptible S. aureus (MSSA)
Clindamycin 600-900 mg IV every 8 hours is the preferred agent because it inhibits bacterial protein synthesis and thereby suppresses exotoxin production 3, 2.
Combine clindamycin with a penicillinase-resistant penicillin (nafcillin or oxacillin 2 g IV every 4 hours) for synergistic bactericidal activity 3.
Alternative for beta-lactam allergy: vancomycin 15-20 mg/kg IV every 8-12 hours plus clindamycin 3.
For Methicillin-Resistant S. aureus (MRSA)
Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS clindamycin 600-900 mg IV every 8 hours provides both bactericidal activity and toxin suppression 3, 2.
Linezolid 600 mg IV every 12 hours is an alternative that also inhibits protein synthesis, though clinical experience in TSS is limited 3, 2.
When Cephalexin IS Appropriate (Not for TSS)
Cephalexin remains highly effective for uncomplicated skin and soft tissue infections caused by MSSA or streptococci, with cure rates ≥90% 4:
Standard Adult Dosing
- Cephalexin 500 mg orally every 6 hours (four times daily) for 5 days for typical cellulitis or skin infections 5, 4.
Pediatric Dosing
- 25-50 mg/kg/day divided into 3-4 doses for children with MSSA infections 6, 4.
- Twice-daily dosing: 22-45 mg/kg/dose for MSSA with MIC 1-2 mg/L; 80 mg/kg/dose for MIC 4 mg/L 6.
- Thrice-daily dosing: 15-25 mg/kg/dose for MSSA with MIC 1-2 mg/L; 45 mg/kg/dose for MIC 4 mg/L 6.
Renal Dose Adjustment
- No adjustment needed for GFR ≥59 mL/min; standard 500 mg every 6 hours 5.
- For severe renal impairment (CrCl <30 mL/min): reduce dose or extend interval based on creatinine clearance 2.
Beta-Lactam Allergy Considerations
- Cephalexin can be used in patients with non-immediate penicillin allergy (e.g., delayed rash), as cross-reactivity is only 2-4% 5.
- Avoid in immediate-type penicillin allergy (urticaria, angioedema, anaphylaxis); use clindamycin 300-450 mg orally every 6 hours instead 5, 2.
Critical Pitfalls to Avoid
Never use cephalexin for suspected or confirmed TSS—it lacks toxin-suppressing activity and may worsen outcomes 1.
Do not use cephalexin for MRSA infections—it has no activity against methicillin-resistant strains 2, 4.
Cephalexin is NOT appropriate for surgical prophylaxis in nasal procedures where TSS risk exists; use anti-staphylococcal agents with toxin-suppressing properties 7, 1.