36-08: Mucormycosis

General Considerations

The term “mucormycosis” is applied to opportunistic infections caused by members of the genera Rhizopus, Mucor, Lichtheimia (formerly Absidia), and Cunninghamella. Predisposing conditions include hematologic malignancy, stem cell transplantation, solid organ transplantation, diabetic ketoacidosis, chronic kidney disease, and treatment with desferoxamine, corticosteroids, or cytotoxic drugs.

Clinical Findings

Invasive disease of the sinuses, orbits, and the lungs may occur. Necrosis is common due to hyphal tissue invasion that may manifest as ulceration of the hard palate, nasal palate, or hemoptysis. Widely disseminated disease can occur. No biochemical assays aid in diagnosis, and blood cultures are unhelpful. Molecular identification (eg, PCR) from tissue and/or mass spectrometry-base detection of a panfungal serum disaccharide may be helpful in specialized centers. A reverse “halo sign” (focal area of ground glass diminution surrounded by a ring of consolidation) may be seen on chest CT. Biopsy of involved tissue remains the cornerstone of diagnosis; the organisms appear in tissues as broad, branching nonseptate hyphae. Cultures are frequently negative.

Treatment

Optimal therapy of mucormycosis involves reversal of predisposing conditions (if possible), surgical debridement, and prompt antifungal therapy. A prolonged course of a lipid preparation of intravenous liposomal amphotericin B (5–10 mg/kg with higher doses given for CNS disease) should be started early. Oral posaconazole (300 mg/day) or isavuconazole (200 mg every 8 hours for 1–2 days, then 200 mg daily thereafter) can be used for less severe disease, as step-down therapy after disease stabilization, or as salvage therapy due to poor response to or tolerance of amphotericin. In patients with breakthrough invasive mold infections despite mold-active antifungal prophylaxis, clinicians should initiate treatment with a different class of antifungal agents than was used for prophylaxis. Combination therapy with amphotericin and posaconazole is not proven but is commonly used because of the poor response to monotherapy. Other azoles are not effective. There are limited data suggesting beneficial synergistic activity when amphotericin and caspofungin are used in combination for rhino-orbital mucormycosis in diabetic patients. Despite favorable animal studies, a pilot study in humans incorporating adjunctive iron chelation therapy with deferasirox demonstrated a higher mortality rate than antifungal therapy alone. Control of diabetes and other underlying conditions, along with extensive repeated surgical removal of necrotic, nonperfused tissue, is essential. Even when these measures are introduced in a timely fashion, the prognosis remains guarded.