Approach to Mucormycosis Caused by Rhizopus
Immediately initiate liposomal amphotericin B at 5-10 mg/kg/day combined with aggressive surgical debridement while simultaneously reversing underlying predisposing conditions—this triple approach is essential for survival. 1
Immediate First-Line Treatment
Antifungal Therapy
- Start liposomal amphotericin B (L-AmB) at a minimum of 5 mg/kg/day immediately upon diagnosis 1, 2
- For CNS involvement, escalate to 10 mg/kg/day 2
- Administer the full daily dose from day one—do not gradually escalate over several days 2
- Amphotericin B lipid complex (ABLC) at 5 mg/kg/day is an acceptable alternative for non-CNS disease 1, 2
- Avoid amphotericin B deoxycholate due to severe adverse effects, particularly nephrotoxicity 1
- The FDA specifically approves amphotericin B for mucormycosis due to Rhizopus species 3
Surgical Management
- Perform surgical debridement in addition to antifungal therapy—this is strongly recommended (AII evidence) 1, 2
- Surgery is particularly critical for:
- For disseminated disease, surgery should be considered on a case-by-case basis using a multidisciplinary approach 1
Reversal of Predisposing Conditions (Strongly Recommended - AII)
- In diabetic patients: Rapidly correct hyperglycemia and ketoacidosis 1, 2
- In neutropenic patients: Administer G-CSF or GM-CSF 1
- Discontinue or minimize corticosteroids to the lowest dose required 1, 2
- Taper other immunosuppressive medications if clinically feasible 2
- Do NOT use deferasirox in hematological patients (AI recommendation against) 1, 2
Diagnostic Confirmation
Microbiological Methods
- Obtain direct microscopy using optical brighteners, histopathology, and culture (strongly recommended) 1
- Identify pathogen to species level using molecular methods 1
- Perform susceptibility testing primarily for epidemiological purposes—using MICs to guide individual treatment has only marginal support 1
Imaging
- Obtain imaging to determine the extent of disease (strongly recommended) 1
- In hematological malignancy and stem cell transplant recipients, look for the reverse halo sign on CT to differentiate mucormycosis from aspergillosis (moderate strength recommendation) 1
Salvage and Second-Line Treatment
When First-Line Fails or Is Intolerated
- Posaconazole 400 mg twice daily is strongly recommended for salvage therapy (BII evidence) 1, 2
- Combination therapy options include:
- The clinical significance of combination therapy data remains uncertain, though animal models show some benefit 1
Agents to Avoid
- Fluconazole, voriconazole, echinocandins as monotherapy, and flucytosine lack meaningful activity against Mucorales 1
- Isavuconazole showed 38% all-cause mortality through Day 42 in mucormycosis patients, with only 31% overall response success 4
Treatment Duration and Monitoring
- Continue treatment until complete response on imaging AND permanent reversal of predisposing factors (strongly recommended) 1, 2
- Consider maintenance therapy with posaconazole after initial treatment (BIII evidence) 1, 2
- Median treatment duration in clinical studies was 102 days for primary therapy 4
Critical Pitfalls to Avoid
- Do not delay treatment—mucormycosis is a fungal emergency where early treatment drives individual prognosis 1
- Do not use monotherapy without addressing underlying conditions—reversal of predisposing factors is as critical as antifungal therapy 1
- Do not rely on antifungal susceptibility testing to guide individual treatment decisions—this has only marginal support 1
- Do not use hyperbaric oxygen as primary therapy—it has only marginal strength support as adjunctive treatment 1
Efficacy Data
- Survival rates with L-AmB are significantly better than conventional amphotericin B: 67% vs 39% (P=0.02) in patients with hematological malignancies 1, 2
- Overall mortality remains high at 24-49% even with optimal treatment 1
- Amphotericin B shows excellent in vitro activity with most Rhizopus strains displaying MICs ≤1 mg/mL 1, 2