36-08: Mucormycosis

ESSENTIALS OF DIAGNOSIS

GENERAL CONSIDERATIONS

The term “mucormycosis” is applied to opportunistic infections caused by members of the genera Rhizopus, Mucor, Lichtheimia (formerly Absidia), Saksenaea, Apophysomyces, and Cunninghamella. Predisposing conditions include hematologic malignancy; hematopoietic or solid organ transplantation; diabetes; iron overload; or treatment with desferoxamine, corticosteroids, or cytotoxic drugs. COVID-19 has been associated with increased rates of mucormycosis, particularly rhino-orbital-cerebral disease. Immunocompetent patients may develop infection due to direct inoculation of wounds such as due to trauma or burns.

CLINICAL FINDINGS

Invasive disease of the sinuses, orbits, and the lungs may occur. The site of infection correlates with the predisposing condition. Diabetes is associated with rhino-orbital-cerebral disease, while hematologic malignancy predisposes to pulmonary infection. Necrosis is common due to hyphal tissue invasion that may manifest as ulceration of the palate or hemoptysis. Widely disseminated disease can occur. Biopsy of involved tissue remains the cornerstone of diagnosis; the organisms appear in tissue as broad, branching nonseptate hyphae. Molecular identification (eg, PCR) from tissue or blood may aid in the diagnosis; cultures are frequently negative. A reverse “halo sign” (focal area of ground-glass diminution surrounded by a ring of consolidation) may be seen on chest CT.

TREATMENT

Optimal therapy of mucormycosis involves reversal of predisposing conditions (if possible), surgical debridement, and prompt antifungal therapy. A prolonged course 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 or isavuconazole is not proven but is commonly used because of the poor response to monotherapy. There are limited data suggesting beneficial synergistic activity when amphotericin and caspofungin are used in combination for rhino-orbital mucormycosis in patients with diabetes. 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.