What is the next best treatment option for a skin infection unresponsive to doxycycline, with an allergy to Keflex (Cephalexin) and no response to Bactrim (Trimethoprim/Sulfamethoxazole)?

Treatment for Skin Infection Unresponsive to Multiple Antibiotics

For a skin infection that has not responded to doxycycline and Bactrim, with an allergy to Keflex, linezolid is the recommended treatment option due to its excellent coverage against resistant organisms including MRSA.

Antibiotic Selection Algorithm

When faced with a skin infection that has failed multiple antibiotic therapies, the following considerations should guide treatment:

Assessment of Current Situation

• Patient has failed treatment with:
  • Doxycycline (a tetracycline)
  • Trimethoprim/sulfamethoxazole (TMP-SMX, Bactrim)
• Patient has an allergic reaction (itching) to cephalexin (Keflex)

Recommended Treatment Options

1. First Choice: Linezolid

   • Highly effective for skin and soft tissue infections (SSTIs)
   • Active against MRSA and other resistant organisms
   • Available in both oral and IV formulations
   • Recommended by multiple guidelines for SSTIs 1
   • Dosing: 600mg orally twice daily for 7-14 days (individualize based on clinical response)

2. Alternative Options:

   • Clindamycin (if no resistance suspected)

     • Effective for both streptococcal and staphylococcal infections 1, 2
     • Caution: Increasing resistance rates in some areas

   • Macrolides (e.g., azithromycin)

     • Recommended for patients with serious penicillin allergy 1
     • May be effective when other options have failed

   • Daptomycin (for severe infections requiring IV therapy)

     • 10 mg/kg/dose IV once daily 1
     • Highly effective against resistant gram-positive organisms

Rationale for Recommendation

The failure of both doxycycline and TMP-SMX suggests possible resistance, particularly if MRSA is involved. The 2018 WSES/SIS-E consensus conference recommends linezolid as a first-line oral agent for MRSA skin infections 1. Linezolid has excellent tissue penetration and bioavailability, making it highly effective for complicated skin infections.

Important Considerations

• Potential MRSA Infection: When multiple antibiotics have failed, consider MRSA as a possible pathogen. The failure of TMP-SMX is particularly concerning as it's typically effective against community-acquired MRSA 1, 3.

• Wound Management: Ensure proper wound care and drainage if indicated. The 2017 pediatric guidelines emphasize that adequate drainage is essential for treatment success in skin infections 1.

• Duration of Therapy: 7-14 days is typically recommended, but should be based on clinical response 1.

• Monitoring: Watch for improvement within 48-72 hours of starting the new antibiotic. If no improvement occurs, reassess the diagnosis and consider obtaining cultures if not already done 2.

Caveats and Pitfalls

• Culture and Susceptibility: Ideally, obtain cultures before starting new antibiotics to guide therapy.

• Cross-Reactivity Concerns: Since the patient has an allergy to cephalexin, avoid other cephalosporins. According to guidelines, up to 10% of penicillin-allergic patients may also be allergic to cephalosporins 2.

• Resistance Patterns: Local antibiotic resistance patterns should be considered when selecting therapy.

• Underlying Conditions: Assess for underlying conditions that might contribute to treatment failure, such as immunosuppression or foreign bodies.

By following this approach and selecting linezolid as the next treatment option, you provide the best chance of successfully treating this resistant skin infection while avoiding medications that have already failed or caused allergic reactions.