What is the treatment for a severe fungal infection characterized by mats of fungus underneath the skin and mycelium biofilms?

Treatment of Severe Fungal Infections with Mats of Fungus Under Skin and Mycelium Biofilms

For severe fungal infections characterized by mats of fungus underneath the skin and mycelium biofilms, immediate treatment with liposomal amphotericin B 5-10 mg/kg per day is strongly recommended as first-line therapy, followed by long-term oral azole therapy.

Initial Assessment and Diagnosis

• Aggressive diagnostic approach is essential:
  • Obtain tissue samples through aspiration and/or biopsy of skin and soft tissue lesions
  • Submit specimens for cytological/histological assessment, microbial staining, and cultures 1
  • Blood cultures should be obtained if systemic infection is suspected

Treatment Algorithm

First-Line Treatment

1. Initial Therapy (Severe Infection):

   • Liposomal amphotericin B 5-10 mg/kg per day IV 1
   • Full daily dose should be given from the first treatment day
   • Continue for 1-2 weeks or until clinical improvement is noted

2. Follow-up Therapy:

   • Transition to oral azole therapy after initial response:
     • Itraconazole 200 mg 3 times daily for 3 days, then 200 mg twice daily 1
     • Voriconazole may be considered for specific fungi (especially Aspergillus, Scedosporium, or Fusarium) 1, 2
     • Posaconazole is an alternative for Mucor/Rhizopus infections 1

3. Duration of Treatment:

   • Minimum treatment duration of 6-12 months 1
   • Continue until complete resolution of lesions and clinical symptoms
   • For extensive or deep tissue involvement, treatment may need to be extended beyond 12 months

Special Considerations

• For CNS Involvement:

  • Liposomal amphotericin B at 10 mg/kg per day is recommended 1
  • Follow with high-dose fluconazole (800 mg daily), itraconazole (200 mg 2-3 times daily), or voriconazole (200-400 mg twice daily) for at least 12 months 1

• For Mucormycosis:

  • Surgical resection of infected tissue in addition to antifungal therapy is strongly recommended 1
  • Continue or restart the last effective antifungal drug for secondary prophylaxis in immunosuppressed patients 1

• For Candida Biofilms:

  • Echinocandins are recommended (e.g., caspofungin, micafungin) 1
  • For Candida parapsilosis, lipid formulation amphotericin B is preferred 1

Surgical Management

• Surgical intervention should be considered for:
  • Extensive or progressive infection
  • Necrotic tissue
  • Persistent symptoms despite antifungal therapy
  • Cavitary lesions present for more than 2 years 1
  • Lesions immediately adjacent to vital structures

Monitoring and Follow-up

• Monitor renal function during amphotericin B therapy
• If substantial renal toxicity develops, dose reduction may be necessary, but doses below 5 mg/kg per day are less effective 1
• Serum levels of azoles (especially itraconazole) should be determined after at least 2 weeks of therapy to ensure adequate drug exposure 1
• Regular clinical assessment for treatment response and adverse effects

Treatment Pitfalls and Caveats

1. Delayed Treatment: Do not delay antifungal therapy while awaiting culture results in suspected cases, as this can lead to increased morbidity and mortality 1

2. Inadequate Dosing: Suboptimal dosing can lead to treatment failure and development of resistance 3

3. Insufficient Duration: Premature discontinuation of therapy before complete resolution can lead to relapse 4

4. Biofilm Considerations: Fungal biofilms are inherently resistant to many antifungal agents, requiring higher doses and longer treatment durations 5

5. Drug Interactions: Azoles inhibit CYP3A4 and can interact with many medications; dose adjustments may be necessary 1

6. Immunosuppression: In immunocompromised patients, more aggressive and prolonged therapy is often required 1

By following this treatment approach, the best outcomes in terms of reducing morbidity, mortality, and preserving quality of life can be achieved for patients with severe fungal infections characterized by mats of fungus under the skin and mycelium biofilms.