What is the treatment for a biopsy-proven fungal skin infection that hasn't resolved with terbinafine (antifungal medication)?

Treatment for Biopsy-Proven Fungal Skin Infection Resistant to Terbinafine

For a biopsy-proven fungal skin infection that hasn't responded to terbinafine, itraconazole should be considered the next treatment of choice due to its broader spectrum of activity against various fungi including dermatophytes, yeasts, and some nondermatophyte molds.

Treatment Algorithm Based on Fungal Type

For Dermatophyte Infections

• Terbinafine is typically first-line therapy for dermatophytes with higher cure rates than other antifungals 1
• For terbinafine-resistant cases, switch to itraconazole 200 mg daily for 12 weeks continuously or as pulse therapy (400 mg daily for 1 week per month) 1
• Itraconazole has broader spectrum activity than terbinafine and is effective against many terbinafine-resistant fungi 1

For Candida Infections

• Itraconazole should be considered first-line treatment for Candida onychomycosis and skin infections resistant to terbinafine 1
• Recommended dosage: 200 mg daily continuously or 400 mg daily for 1 week per month (pulse therapy) 1
• Fluconazole can be used as an alternative if itraconazole is contraindicated 1

For Nondermatophyte Mold Infections

• Itraconazole has broader antimicrobial coverage for nondermatophyte molds compared to terbinafine 1
• For severe or resistant cases, consider newer azoles such as voriconazole or posaconazole which have activity against a wider range of fungi 2

Medication Details and Considerations

Itraconazole

• Mechanism: Inhibits fungal cell wall ergosterol synthesis 1
• Dosage: 200 mg daily for 12 weeks continuously or 400 mg daily for 1 week per month 1
• Advantages: Active against a range of fungi including yeasts, dermatophytes, and some nondermatophyte molds 1
• Monitoring: Liver function tests recommended for treatment durations longer than 1 month 1
• Contraindications: Pregnancy, certain cardiac conditions 1
• Drug interactions: Multiple significant interactions with anticoagulants, antihistamines, antipsychotics, and other medications 1

Alternative Options

• For cases with suspected mixed infections, combination therapy may be appropriate 2
• For Candida-associated paronychia, consider topical imidazole lotions alternating with antibacterial solutions 3
• For severe or refractory cases, consider newer antifungals such as voriconazole or posaconazole 2

Important Considerations and Pitfalls

• Confirm the fungal species through culture before switching therapy, as treatment should be tailored to the specific pathogen 1
• Evaluate for factors that might contribute to treatment failure:
  • Incorrect diagnosis or mixed infection 1
  • Poor medication adherence 1
  • Immunosuppression 1
• Treatment duration may need to be extended in resistant cases 1
• Re-evaluate 3-6 months after treatment initiation and consider further treatment if the infection persists 1
• Be aware that long-term follow-up is necessary as relapse can occur even after apparent cure 1

Special Situations

• For paronychia with fungal involvement, implement antiseptic soaks with dilute vinegar and consider combination therapy with antifungals and anti-inflammatory agents 3
• For widespread or severe infections, systemic therapy is preferred over topical treatments 4
• For nail infections, topical therapy alone is often ineffective due to poor penetration through the nail plate 4