- Author: Nancy F Crum-Cianflone, MD, MPH; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD more...
Antifungal treatment consists of lipid formulations of amphotericin (eg, liposomal amphotericin), amphotericin B deoxycholate, or posaconazole. Although most clinical experience has focused on amphotericin agents, data on the efficacy of posaconazole are promising. This agent may eventually become the drug of choice, but more evaluation is needed.
Amphotericin B has proven efficacy in the treatment of mucormycosis, and the conventional form (deoxycholate) is typically administered at 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.
A lipid formulation of amphotericin B has now replaced amphotericin B deoxycholate as the drug of choice, owing to improved efficacy and safety of these formulations (eg, AmBisome). Lipid preparations of amphotericin B are typically used at 5 mg/kg/d. Some have used doses of up to 15 mg/kg/d to treat mucormycosis, although the clinical advantages of higher doses are unknown.
Posaconazole, a triazole, is currently considered a second-line drug for treatment of mucormycosis, and the typical dose is 400 mg orally twice daily (total of 800 mg/d). Since achieving steady-state plasma concentrations of this drug takes approximately 1 week, most experts would not recommend using this agent for initial treatment, but rather initially administering intravenous liposomal amphotericin B. Sequential therapy by first using liposomal amphotericin followed later by posaconazole has been used.[40, 41] Since posaconazole is only available in an oral formulation, absorption is an important consideration; administration with high-fat food or acidic beverage and the avoidance of antacids is advised.
Studies have reported that posaconazole yielded a 50-70% success rate, whereas the comparator (typically amphotericin B or lipid-based amphotericin, in many cases used as salvage therapy) yielded a success rate of only 25%, which suggests that posaconazole may become the preferred drug for mucormycosis. A recent review of 96 cases treated between 2003 and 2011 with posaconazole found that complete response was achieved in 62 (64.6%), partial response in 7 (7.3%) patients, and stable disease in 1 (1%), with an overall mortality of 24% (no data for 3 patients). However, further studies are needed.[53, 54]
Posaconazole has also been studied in several case reports, including as salvage therapy after failure of amphotericin B therapy. 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.
Most commonly, posaconazole is used as sequential therapy after the initial administration and control of the disease with liposomal amphotericin B.[40, 41]
Isavuconazole (Cresemba) is a triazole antifungal agent. Isavuconazole is the active moiety of the prodrug isavuconazonium sulfate. It is indicated for invasive mucormycosis infection caused by Mucorales fungi (eg, R oryzae, Mucormycetes species).
Isavuconazole’s approval in March 2015 was based on an open-label noncomparative study in adult patients with invasive aspergillosis and renal impairment or in patients with invasive fungal disease caused by other rare fungi. A subpopulation of 37 patients with invasive mucormycosis treated with isavuconazole showed all-cause mortality was 38%. The efficacy of isavuconazole in the treatment of invasive mucormycosis has not been evaluated in concurrent, controlled clinical trials.
Other azoles (eg, fluconazole, voriconazole) have not shown significant activity against these fungi. Of note, despite the use of voriconazole prophylaxis in high-risk patients (eg, transplant recipients), breakthrough zygomycosis has been reported.[43, 44, 45]
Animal and limited clinical data suggest that combination therapy with lipid formulations 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.[46, 33, 47]
Antifungal agents are used to treat Mucorales infection. The mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
Liposomal amphotericin B is amphotericin B encapsulated in a bilayer of liposomes. This antifungal agent is considered first-line therapy for mucormycosis. It should also be used in the setting of preexisting renal dysfunction, when renal toxicity develops during amphotericin B deoxycholate therapy, or when amphotericin B deoxycholate therapy is failing. Nephrotoxicity and infusion-related toxicity are reduced compared with conventional amphotericin B deoxycholate.
Amphotericin B is the drug of choice (DOC) to treat most fungal infections. Amphotericin B deoxycholate is produced by a strain of Streptomyces nodosus and can be fungistatic or fungicidal. Amphotericin B binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death. This agent is active against mucormycosis, Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, Candida species, and Aspergillus species.
Amphotericin B lipid complex is amphotericin B in phospholipid complexed form. This is an alternate therapy to liposomal amphotericin B.
Posaconazole is a triazole antifungal agent that blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Posaconazole is available as an oral suspension (200 mg/5 mL).
Posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression. This agent has also been used for serious fungal infections (eg, mucormycosis, invasive aspergillosis, Fusarium infection, Scedosporium apiospermum infection, candidemia, candidiasis).
Triazole antifungal agent. Isavuconazole is the active moiety of the prodrug isavuconazonium sulfate. It is indicated for invasive mucormycosis infection caused by Mucorales fungi (eg, R oryzae, Mucormycetes species).
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