Is Keflex (Cephalexin) effective against Staphylococcus infections?

Effectiveness of Keflex (Cephalexin) Against Staphylococcus Infections

Yes, Keflex (cephalexin) is effective against methicillin-susceptible Staphylococcus aureus (MSSA) infections, but it is not effective against methicillin-resistant Staphylococcus aureus (MRSA).

Mechanism and Spectrum of Activity

Cephalexin is a first-generation cephalosporin that works by inhibiting bacterial cell wall synthesis. According to the FDA drug label, cephalexin has demonstrated activity against Staphylococcus aureus, including penicillinase-producing strains 1. However, the label specifically notes that methicillin-resistant staphylococci are resistant to cephalosporins, including cephalexin.

Effectiveness Against Different Staphylococcal Infections

Skin and Soft Tissue Infections (SSTIs)

• Cephalexin is recommended by the Infectious Diseases Society of America (IDSA) for treating impetigo caused by Staphylococcus aureus at a dose of 250 mg four times daily for adults or 25-50 mg/kg/day in 3-4 divided doses for children 2
• For methicillin-susceptible S. aureus (MSSA) skin and soft tissue infections, cephalexin is recommended at 500 mg four times daily 2
• Clinical studies have shown cure rates of 90% or higher for staphylococcal skin infections treated with cephalexin 3

MRSA Infections

• Cephalexin has no activity against MRSA 1, 4
• For suspected or confirmed MRSA infections, alternative antibiotics such as trimethoprim-sulfamethoxazole, clindamycin, doxycycline, or linezolid should be used 2, 5

Comparative Effectiveness

A randomized controlled trial comparing cephalexin with clindamycin for uncomplicated pediatric skin infections found no significant difference in clinical improvement rates (94% vs 97% at 48-72 hours), even though 69% of the infections were caused by MRSA 6. This surprising finding may be attributed to:

• Proper incision and drainage procedures performed in 97% of subjects
• Close follow-up and wound care being more important than antibiotic choice for properly drained, uncomplicated SSTIs

Another study comparing cefdinir to cephalexin for mild to moderate uncomplicated skin infections found similar clinical cure rates (89% for both treatments) 7.

Clinical Applications and Dosing

For staphylococcal infections where MSSA is confirmed or highly suspected:

• Adults: 500 mg orally four times daily
• Children: 25-50 mg/kg/day in 4 divided doses orally
• Duration: Typically 7-10 days depending on infection severity and clinical response

Important Considerations and Pitfalls

1. Always consider local resistance patterns: In areas with high MRSA prevalence, empiric therapy with cephalexin alone may be inadequate

2. Obtain cultures when appropriate: For recurrent or non-responsive infections, cultures should guide therapy

3. Proper adjunctive therapy: For abscesses, incision and drainage remains the primary treatment, with antibiotics as adjunctive therapy 2

4. Cross-reactivity with penicillin allergy: Cephalexin should be avoided in patients with immediate hypersensitivity reactions to penicillins (urticaria, angioedema, bronchospasm, or anaphylaxis) 4

5. Monitor for clinical response: If no improvement is seen within 48-72 hours, reevaluate diagnosis and consider alternative antibiotics

Alternative Options When Cephalexin Is Not Appropriate

For MRSA infections or when cephalexin is contraindicated:

• Clindamycin: 300-450 mg orally four times daily (adults)
• Trimethoprim-sulfamethoxazole: 1-2 double-strength tablets twice daily (adults)
• Doxycycline: 100 mg twice daily (adults, not for children <8 years)
• Linezolid: For more severe infections

In summary, cephalexin remains an effective option for MSSA infections but should not be used as monotherapy when MRSA is suspected or confirmed.