Medication Summary
Start antifungal therapy as early as possible. [18, 14] Until recently, amphotericin B was the only available antifungal with some proven efficacy against most of the Zygomycetes. Recently, a novel azole antifungal, isavuconazonium sulfate (isavuconazole) has been approved for the treatment of invasive mucormycosis. [19, 20]
Lipid preparations of amphotericin B have been the current mainstay of therapy for all forms of mucormycosis. [5, 18, 21] The lipid preparations of amphotericin B are used more frequently because they allow the delivery of higher doses of the parent compound, amphotericin B. In addition, lipid preparations cause milder renal insufficiency typically associated with amphotericin B. Although investigational, combination therapy with lipid preparations of amphotericin B and G-CSF have been successful in several small-scale clinical trials. [22] Additionally, other combinations that have shown some synergistic activity include amphotericin B and echinocandins, amphotericin B and posaconazole, and amphotericin B and isavuconazole. [23]
Isavuconazole, a newer triazole, was recently approved by the FDA for the treatment of invasive aspergillosis and invasive mucormycosis. [19, 20] It has quickly become a viable alternative as primary therapy for invasive mucormycosis. The antifungal is available in capsule form, 186 mg of isavuconazonium sulfate (equivalent to 100 mg isavuconazole), and parenteral form, 372 mg of isavuconazonium sulfate (equivalent to 200 mg isavuconazole). The drug has demonstrated excellent results in a large multicenter, open-label study.
Posaconazole is also a triazole with proven efficacy against most Zygomycetes in vitro and in vivo. [24, 25, 26] Posaconazole was approved with an indication for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression. [26] Currently, posaconazole is available in an oral suspension, a tablet, and, most recently, in parenteral form and must be administered 2-4 times per day. It has shown encouraging results in open-labeled clinical trials involving complicated Zygomycetes infections. [27] In addition, posaconazole is frequently used as the oral de-escalation therapy in patients in whom amphotericin B has elicited an initial response and are clinically stable or improving.
Antifungals
Class Summary
These agents are polyene antifungals. [28] They represent the only antifungal class with known activity against Zygomycetes.
The FDA has approved 3 novel lipid formulations of amphotericin B. The advantage of the lipid preparation over standard amphotericin B deoxycholate is that it delivers higher concentrations of amphotericin B, resulting in a theoretical increase in therapeutic potential and causes decreased nephrotoxicity (25%). The 3 lipid formulations include amphotericin B lipid complex (ABLC; Abelcet), amphotericin B colloidal dispersion (ABCD; Amphotec), and liposomal amphotericin B (L-AMB; AmBisome).
Amphotericin B (Amphocin, Fungizone)
The only available antifungal agent effective against Zygomycetes. Because of the drug toxicity, monitoring for side effects and toxicity is extremely important. Dose aggressively. A polyene antibiotic synthesized by Streptomyces nodosus. Binds irreversibly to ergosterol in fungal cell membrane. This increases permeability and causes extracellular leak of cations and eventual cellular death.
Amphotericin B lipid complex (Abelcet)
Mainstay of therapy in any form of zygomycosis. Approved for treating adults and children with fungal infections refractory to, or intolerant of, conventional amphotericin B.
Amphotericin B colloidal dispersion (Amphotec)
Approved for treating adults and children with aspergillosis refractory to, or intolerant of, conventional amphotericin B.
Liposomal amphotericin B (AmBisome)
Mainstay of therapy for any form of zygomycosis. It is approved for the treatment of adults and children with aspergillosis, candidiasis, and cryptococcosis refractory to, or intolerant of, conventional amphotericin B. Also approved for empiric antifungal therapy of persistently febrile neutropenic patients.
Antifungal agents, triazoles
Class Summary
Posaconazole has shown encouraging results in clinical trials for complicated Zygomycetes infections.
Posaconazole (Noxafil)
Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. In vitro, posaconazole has demonstrated activity against most Zygomycetes. This mechanism of action results in the disruption of the cellular membrane. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression and for the treatment of oropharyngeal candidiasis and antifungal refractory oropharyngeal candidiasis.
Systemic, Antifungal agent, triazole
Isavuconazonium sulfate (Cresemba, Isavuconazole)
Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. In vitro, isavuconazole has demonstrated excellent activity against the Mucormycetes. This mechanism of action results in the disruption of the cellular membrane. Available as a capsule (186 mg isavuconazonium sulfate, equivalent to 100 mg of isavuconazole) and parenteral formulation (372 mg isavuconazonium sulfate, equivalent to 200 mg isavuconazole). It is approved for invasive mucormycosis and invasive aspergillosis.
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A 45-year-old woman with poorly controlled diabetes mellitus with facial and periorbital swelling due to zygomycosis. She was unable to open her right eye upon admission.
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Material from the periorbital tissue of a woman with poorly controlled diabetes mellitus with facial and periorbital swelling due to zygomycosis is stained with periodic acid-Schiff stain (X 560). The material demonstrates the classic appearance of irregularly shaped broad hyphae with right-angle branching (arrow).
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A CT scan of the head of a patient with zygomycosis shows involvement of the paranasal sinuses and periorbital soft tissues.
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A 60-year-old woman with diabetes mellitus and 5 days post operative from resection of a benign pituitary tumor. The lesion developed over the surgical scar. Biopsy of lesion demonstrated invasive cutaneous mucormycosis.
