Zygomycosis Medication

Start antifungal therapy as early as possible. Amphotericin B is the only available antifungal that has some proven efficacy against the Zygomycetes. Because of drug toxicity, monitor for adverse effects and toxicity. Lipid preparations of amphotericin B are the current mainstay of therapy for all forms of zygomycosis.^{[10, 4]} 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 still investigational, combination therapy with lipid preparations of amphotericin B and G-CSF have been successful in several studies.

In addition, a new triazole, posaconazole, was recently approved by the US Food and Drug Administration (FDA). Posaconazole has proven efficacy against most Zygomycetes in vitro and in vivo.^{[13, 14, 15]} Posaconazole was approved with an indication for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.^[15] Eventually, posaconazole may replace amphotericin B compounds as the drug of choice for zygomycosis. Posaconazole is available only in an oral suspension and must be administered 2-4 times per day. It has shown encouraging results in open-labeled clinical trials involving complicated Zygomycetes infections.^[16] Posaconazole is frequently used as oral de-escalation therapy in patients in whom amphotericin B has elicited an initial response.

Class Summary

These agents are polyene antifungals. 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.

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 (Sun, 2002; Dannaoui, 2003). 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.