Table 2.

Anti-fungal strategies for mucormycosis.

Therapy	Anti-Fungal Strategies	Pros and Cons	Mode of Action
Established therapies	Amphotericin B (AmB) deoxycholate	Toxicity	Depending on the concentration in body fluids and the susceptibility of the fungus, amphotericin B is either fungistatic or fungicidal. The medicine works by binding to sterols (ergosterol) in susceptible fungi’s cell membranes. This results in the formation of a transmembrane channel and a change in membrane permeability, which allows intracellular components to seep out. Amphotericin B and azoles act on ergosterol, the most abundant sterol in the fungus cytoplasmic membrane. Amphotericin B is a polyene that binds permanently to ergosterol, causing membrane rupture and cell death [74].
	Liposomal amphotericin B	Less toxic than AmB, most expensive polyene	Also acts by binding the sterols in fungal cell membrane. Binding cell membrane can cause alterations in cell permeability and also causes cell death [75].
	Amphotericin B lipid complex	Less toxic than AmB	Acts by binding to sterols in fungal cell membrane.
Investigational/adjunctive therapies	Itraconazole (Figure 7)	Superior toxicity profile	14-demythalase, a cytochrome P-450 enzyme required for the conversion of lanosterol to ergosterol, interacts with itraconazole. Because ergosterol is a necessary component of the fungal cell membrane, inhibiting its production causes increased cellular permeability, resulting in cellular contents leakage. Itraconazole can also decrease endogenous respiration, interact with membrane phospholipids, prevent yeasts from transforming into mycelial forms, prevent purine uptake, and affect triglycerides and phospholipid production [76].
	Posaconazole	More effective than itraconazole in animal models	Posaconazole is a triazole antifungal drug that works by blocking the cytochrome P-450 dependent enzymes sterols 14 demythalase in fungi by attaching to the heme co factor present on the enzymes [77]. This causes the synthesis of ergosterol, a critical component of the fungal cell membranes to be inhibited, as well as the accumulation of methylated sterol precursors. As a result, the fungal cell development is inhibited and eventually cell death occurs.
	Caspofungin	Very low toxicity, virtually no clinical data for mucormycosis	Caspofungin inhibits the synthesis of beta (1, 3) D-glucan, a key component of the cell wall of Aspergillus species and Candida species. In mammalian cells, beta (1-3)-D glucan is not found. The main target is beta (1,3)-glucan synthase [68].
	Iron chelation	Synergistic with ABLC in murine	Induces iron starvation and thus promotes a fungicidal effect.
	Hyperbaric oxygen	Benefit in combination with anti-fungals	Suppresses fungal growth in vitro, reduces tissue hypoxia and acidosis caused due to fungal invasion.
	Cytokine therapy	Nontoxic, Successful case reports	Cytokines play a key role in signaling molecules that modulate and control immunity, inflammation, and hematopoiesis. Cytokines are a diverse set of proteins, peptides, and glycoproteins released by the immune system of cells [78].