Once invasive fungal elements are confirmed on frozen section, antifungal therapy and surgical debridement should be initiated without delay. Efforts should also be directed toward restoration of immune function, by withdrawing immunosuppressive medications or addressing the predisposing illness.

Amphotericin B continues to be the drug of choice, at doses of 0.8 to 1.5 mg/kg/day. Nephrotoxicity is the dose-limiting factor, but amphotericin B lipid complex can minimize the renal side effects and allow dose escalation up to 5 to 7 mg/kg/day in patients with kidney disease. An alternative agent for zygomycetes is the second-generation triazole posaconazole (23). Itraconazole, voriconazole, and Casopofungin should not be used for rhinocerebral mucormycosis but can be considered for invasive Aspergillus.

Medical therapy alone rarely contains infection, especially in the setting of neutropenia or severe immunosuppression. As a rule, involved tissue should be surgically resected as soon as possible. Transnasal endoscopic surgery, external ethmoidectomy, or a Caldwell-Luc procedure are performed for limited disease; more extensive disease requires radical surgical resection, including medial maxillectomy, total maxillectomy with orbital exoneration, or even more extensive craniofacial resection. In a retrospective analysis performed by Gillespie in 1998, 9 of 10 survivors underwent complete surgical resection. Obvious disease was left behind in nine of nine patients who died of the disease (24). This supports the principle that complete surgical resection is required to obtain a cure.

Systemic antifungal therapy should be continued even if all necrotic tissue is fully debrided, given the high likelihood of unapparent local and disseminated disease (7). In general, therapy should be continued until there is a clear clinical remission and as many immunocompromising conditions as possible are reversed.

Once in remission, patients may be transitioned to oral itraconzole or voriconazole as chronic suppressive therapy. Empiric coverage with amphotericin B should be resumed during subsequent periods of immunocompromise.

Hyperbaric oxygen has been used in some patients with mucormycosis, but no benefit has been demonstrated (25).

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