Mucormycosis Treatment & Management

Patients with mucormycosis should be treated in a tertiary referral center with subspecialty units experienced in the care of the condition and the underlying causes. Correction of the underlying abnormality and prompt institution of liposomal amphotericin B therapy and surgical resection are critical.

Other important considerations in medical management include the following:

• Diabetic ketoacidosis requires insulin, correction of acidosis with sodium bicarbonate, and rehydration
• Neutropenia in association with hematologic malignancy and its treatment should be reversed, if possible, with the use of colony-stimulating factors and the withdrawal of cytotoxic chemotherapy
• Wean glucocorticosteroids and other immunosuppressive drugs
• Interrupt deferoxamine therapy; hydroxypyridine chelating agents may be substituted for deferoxamine

For prevention, avoid the use of contaminated medical bandages and other equipment to prevent cutaneous disease; frequently check the wound(s). The use of contaminated bandages and other dressings has caused cutaneous mucormycosis. Failure to examine areas under dressings or to recognize the significance of deterioration in preexisting wounds may produce severe cutaneous and, ultimately, disseminated disease. Place patients with severe prolonged neutropenia in rooms equipped with high-efficiency particulate air (HEPA) filters, where practicable.

Antifungal treatment consists of lipid formulations of amphotericin B, amphotericin B deoxycholate, or posaconazole. First-line treatment is with an amphotericin derivative.

Liposomal and lipid complex amphotericin B

Amphotericin B has proven efficacy in the treatment of mucormycosis. At the present time, the liposomal formulation (eg, AmBisome) is the drug of choice based on efficacy and safety data.^[11] Lipid preparations of amphotericin B are used at 5 mg/kg/d.^[1] Some have used doses of up to 15 mg/kg/d to treat mucormycosis; however, the benefit of higher doses is unknown.

Amphotericin B

Amphotericin B deoxycholate can also be used for the treatment of mucormycosis, especially in settings of cost restraints. The typical dose is 1-1.5 mg/kg/d. The total dose given over the course of therapy is usually 2.5-3 g. High doses of this drug are required, and nephrotoxicity may result. This is of particular concern since many patients who develop mucormycosis have preexisting renal disease (eg, diabetics, transplant recipients). Monitor the renal function of patients taking amphotericin B; doubling of serum creatinine over the baseline levels is an indication for changing to liposomal amphotericin B.

In addition, careful monitoring and repletion of serum electrolytes (eg, potassium, phosphorus, magnesium) should be performed when administering any formulation of amphotericin B.

Posaconazole

Posaconazole, a triazole, is currently considered a second-line drug for treatment of mucormycosis and the typical dose is 400 mg twice daily (total of 800 mg/d). Administration with a high-fat meal/food enhances absorption of the drug. In addition, therapeutic drug monitoring of posaconazole levels should be considered in patients at high risk for malabsorption (eg, patients with mucositis or GI disease, including graft versus host disease).^[11]

Posaconazole has also been studied in several case reports,^[10] including as salvage therapy after failure of amphotericin therapy.^[12] Rickerts et al reported that liposomal amphotericin B plus posaconazole was successful in the treatment of disseminated mucormycosis in a patient who could not undergo surgery; however, the benefit of dual antifungal therapy is unclear.^[13]

Posaconazole has also been used as sequential therapy after the initial administration and control of the disease with liposomal amphotericin B.^{[14, 15]}

Other azoles

Other azoles (eg, fluconazole, voriconazole) have not shown significant activity against mucormycosis fungi. Of note, despite the use of voriconazole prophylaxis in high-risk patients (eg, transplant recipients), breakthrough zygomycosis has been reported.^{[16, 17, 18]}

Animal and limited clinical data suggest that combination therapy with a lipid formulation of amphotericin and an echinocandin (eg, micafungin, caspofungin) may improve survival; however, more clinical trial data are needed before this strategy can be definitively recommended.^{[11, 19, 20, 21]}

Debridement of necrotic tissue in combination with medical therapy is mandatory for patient survival. In rhinocerebral disease, surgical care includes drainage of the sinuses and may require excision of the orbital contents and involved brain (see the following images). Repeated surgery may be required, especially for rhinocerebral mucormycosis.

Excise pulmonary lesions if they are localized to a single lobe; excise cutaneous lesions entirely, and resect any GI masses.

Patient survival from mucormycosis requires rapid diagnosis and aggressive coordinated medical and surgical therapy. To that effect, consultations with various specialists are critical.

An infectious diseases consultation is warranted for management of antifungal therapy and coordination of medical care.

Surgical specialties consultations depend on the location of disease, as follows:

• Ear, nose, and throat consultation and neurosurgery consultation for rhinocerebral mucormycosis
• Thoracic surgery consultation for pulmonary involvement
• Gastrointestinal (GI) surgery consultation for GI involvement
• Plastic surgery consultation for cutaneous involvement

In addition, endocrinologic consultation may be necessary for the management of unstable diabetes; hematologic/oncologic consultation may be needed for the management of issues related to hematology and solid tumors; and surgical intensive care unit (SICU) consultation is important for supportive care.

Ongoing clinical surveillance and diagnostic imaging are required to ensure complete resolution of mucormycosis and to detect relapse.

Successful courses of therapy typically last 4-6 weeks and require cumulative doses that are equivalent to greater than 2 g of amphotericin B deoxycholate. Posaconazole offers another treatment option. Repeated surgical debridement of necrotic tissue identified by follow-up head computed tomography (CT) scan or magnetic resonance imaging (MRI) is often indicated.

For patients who successfully complete therapy for mucormycosis and who subsequently require immunosuppressive treatments (eg, chemotherapy in a cancer patient), daily oral posaconazole or intermittent amphotericin infusions (once or twice weekly) are often administered in an attempt to prevent relapse of infection, although evidence-based data on the best strategy are currently not available.^[1]

Educate patients about the signs of disease, such as facial swelling and black nasal discharge, and instruct patients to present promptly for evaluation if these signs occur.