What is the treatment for mucormycosis (fungal infection) resistant to Isavuconazole (antifungal medication)?

Treatment of Mucormycosis Resistant to Isavuconazole

For mucormycosis resistant to isavuconazole, liposomal amphotericin B at 5-10 mg/kg/day is strongly recommended as the most effective salvage treatment option, combined with surgical debridement whenever feasible. 1

First-Line Salvage Treatment Options

Liposomal Amphotericin B

• Liposomal amphotericin B should be administered at 5-10 mg/kg/day, with the full daily dose given from the first treatment day (avoid slow dose escalation) 1
• For CNS involvement, use 10 mg/kg/day based on animal models and clinical observations 1
• In non-CNS involvement, 5 mg/kg/day is generally sufficient 1
• Renal function should be closely monitored, as nephrotoxicity is the main limiting factor 1

Alternative Amphotericin B Formulations

• Amphotericin B lipid complex 5 mg/kg/day is moderately recommended for patients without CNS involvement 1
• Amphotericin B colloidal dispersion has shown efficacy as salvage treatment 1
• Conventional amphotericin B deoxycholate should be used only when no other options are available due to substantial toxicity 1, 2

Second-Line Salvage Options

Posaconazole

• Posaconazole delayed release tablets or IV formulation are strongly supported for salvage treatment when amphotericin B formulations cannot be used 1
• Dosing: 300 mg twice daily on day 1, followed by 300 mg daily from day 2 1
• Posaconazole oral suspension (4 × 200 mg/day) is only marginally supported due to variable bioavailability 1

Combination Therapy Approaches

• Limited data support combinations of polyenes and azoles or polyenes plus echinocandins 1
• Consider combination therapy in cases of:
  • Refractory disease despite optimal monotherapy 1
  • Severe or disseminated infections 1
  • Mixed mold infections, particularly in trauma patients 1
• Potential combinations include liposomal amphotericin B with posaconazole 1
• Note that combination therapy has not definitively shown superior outcomes in controlled studies but may be rationally given due to lack of enhanced toxicity 1

Surgical Management

• Surgical debridement with clean margins is strongly recommended whenever feasible 1
• Surgery serves multiple purposes:
  • Disease control 1
  • Obtaining tissue for histopathology 1
  • Microbiological diagnostics 1

Treatment Duration

• Continue treatment until:
  • Complete resolution of clinical signs and symptoms 1
  • Substantial radiographical improvement 1
  • Permanent reversal of underlying immunosuppression 1
• Treatment duration is typically weeks to months (median duration in studies was approximately 84 days) 1
• Intravenous treatment should be continued until stable disease is achieved before considering oral options 1

Monitoring and Follow-up

• Regular assessment of treatment response through clinical evaluation and imaging 1
• Monitor for adverse effects, particularly renal function with amphotericin B formulations 1
• Be aware that radiological assessment may be complicated by scarring and postoperative changes 1

Special Considerations

• Address underlying conditions that predispose to mucormycosis (e.g., control diabetes, reduce immunosuppression if possible) 1
• Be vigilant for late relapses, which have been documented in long-term survivors 1
• Mucormycosis treatment should be considered an emergency requiring rapid action 1

Common Pitfalls to Avoid

• Delaying initiation of salvage therapy once isavuconazole resistance is suspected 1
• Slowly escalating amphotericin B doses instead of starting with the full therapeutic dose 1
• Using amphotericin B deoxycholate when lipid formulations are available 1
• Inadequate surgical debridement 1
• Premature discontinuation of therapy before complete resolution 1