What is the appropriate treatment for an immunocompromised patient with a history of invasive aspergillosis who is now suspected to have Mucormycosis and is currently on voriconazole?

Mucormycosis Treatment in an Immunocompromised Patient Currently on Voriconazole

Immediately discontinue voriconazole and switch to liposomal amphotericin B at 5-10 mg/kg/day, as voriconazole has no activity against Mucorales and continuing it will result in treatment failure and likely death. 1

Critical First Steps

Immediate Antifungal Switch

• Stop voriconazole immediately – this agent is completely inactive against mucormycosis and its continued use represents inadequate therapy 1
• Start liposomal amphotericin B (L-AmB) at 5-10 mg/kg/day as first-line therapy, giving the full dose from day one without gradual escalation 1
• For CNS involvement specifically, use L-AmB at 10 mg/kg/day based on animal models and clinical observations 1
• Amphotericin B lipid complex (ABLC) at 5 mg/kg/day is an alternative if L-AmB is unavailable, though L-AmB is preferred 1

Diagnostic Confirmation While Treating

• Do not delay treatment to obtain tissue diagnosis – immediate empiric therapy is strongly recommended in any immunocompromised patient with suspected mucormycosis 1
• Pursue tissue biopsy urgently for histopathology and culture to confirm diagnosis and identify species 1
• Send tissue samples without homogenization to preserve fungal architecture 2
• Review imaging for the "reversed halo sign" on chest CT (highly suggestive of pulmonary mucormycosis) or MRI for rhinocerebral involvement 3

Surgical Management

Early complete surgical debridement is mandatory and should be performed as soon as medically feasible in addition to antifungal therapy. 1

• Surgical resection or debridement should be repeated as required until all necrotic tissue is removed 1
• Surgery is particularly critical for rhinocerebral disease, skin and soft tissue infections, and pulmonary lesions near great vessels 1
• The combination of surgery plus antifungal therapy yields better outcomes than antifungal therapy alone 1

Reversal of Underlying Risk Factors

Aggressively address all modifiable risk factors, as this is as important as antifungal therapy itself. 1, 3

• Discontinue or taper glucocorticosteroids to the lowest possible dose 1, 3
• Reduce immunosuppressant medications (calcineurin inhibitors, mTOR inhibitors) when feasible 3
• Reverse neutropenia through growth factors or granulocyte transfusions if applicable 3
• Stop deferroxamine immediately if the patient is receiving iron chelation therapy, as this paradoxically increases mucormycosis risk 3
• Optimize diabetes control if present 1

Alternative and Salvage Options

If L-AmB Cannot Be Used

• Isavuconazole is an alternative first-line option with demonstrated efficacy against mucormycosis, approved by the FDA for this indication 1, 4
• Isavuconazole has linear pharmacokinetics with fewer drug interactions than voriconazole and may not require therapeutic drug monitoring 5, 4
• Amphotericin B deoxycholate at 1.0-1.5 mg/kg/day can be used only if lipid formulations are unavailable, but carries substantial nephrotoxicity risk 1

Salvage Therapy

• Posaconazole (delayed-release tablets 300 mg twice daily on day 1, then 300 mg daily) is recommended for salvage therapy or step-down after clinical stabilization 1
• Combination therapy with L-AmB plus an echinocandin (caspofungin) may be considered for salvage, though evidence is limited to case reports and animal models 1, 6
• A combination of L-AmB with deferasirox showed inferior results and should be avoided 1

Duration and Monitoring

• Continue antifungal therapy for a minimum of 6-12 weeks, but duration is ultimately guided by resolution of symptoms, radiographic improvement, and immune reconstitution 1
• Treatment must continue throughout the period of immunosuppression 1
• If substantial renal toxicity develops with L-AmB, the dose can be reduced, but doses below 5 mg/kg/day are only marginally supported 1
• Monitor renal function closely, as doses of 10 mg/kg/day cause substantial but mostly reversible creatinine increases 1

Secondary Prophylaxis

In persistently immunosuppressed patients with successfully treated mucormycosis who require ongoing immunosuppression, restart or continue the last effective antifungal agent as secondary prophylaxis. 1

• Surgical resection of residual disease plus continuation of antifungal therapy is strongly recommended before resuming immunosuppression 1

Critical Pitfalls to Avoid

• Never use voriconazole, itraconazole, or fluconazole for mucormycosis – these azoles lack activity against Mucorales 1
• Do not use echinocandins as monotherapy – they are ineffective against mucorales as primary treatment 1, 4
• Do not slowly escalate amphotericin B dosing – give the full therapeutic dose from day one 1
• Do not delay surgery while waiting for antifungal response – combined medical-surgical approach is essential 1
• Recognize that this patient's history of invasive aspergillosis on voriconazole creates a diagnostic challenge, as breakthrough fungal infection on azole therapy should raise immediate suspicion for mucormycosis 1