Treatment

The role of surgery in the treatment of mucormycosis cannot be overemphasized. Because of their propensity for invading blood vessels, the Mucorales cause extensive tissue infarction, thereby impairing the delivery of antifungal agents to the site of infection. This often leaves surgery as the only modality that may effectively eliminate the invading microorganisms. In one small study of 10 patients with RCM, all patients were noted to have involvement of the pterygopalatine fossa, and it was noted that facial soft tissues, palate, and infratemporal fossa were potentially infected via connecting pathways from the pterygopalatine fossa (12). The study concluded that debridement of the pterygopalatine fossa seems to be a definitive method of managing RCM, based on this limited cohort. In addition, Mohs micrographic surgery has been reported as a tissue-sparing technique in the management of the cutaneous form of mucormycosis. It is important to understand the urgency of surgical resection. This is a true surgical emergency and is an operation that requires immediate attention. A case diagnosed in the late afternoon cannot be scheduled for the following day; rather, it must be operated that evening, even if late at night.

Amphotericin B is the first-line drug of choice for most cases of zygomycosis caused by the Mucorales. Amphotericin mediates its antifungal action by modifying fungal cell walls. This drug binds to ergosterol and causes increased cell wall permeability. With permeabilization, ions leak from the cell and the membrane depolarizes. The maximal tolerated doses are given until progression is halted. Endoscopic examination of paranasal sinuses can help assess progression. With the deoxycholate formulation, a dosage of 1 to 1.5 mg/kg daily is indicated. Amphotericin B lipid complex or liposomal amphotericin B, each at 5 mg/kg daily, appear to be as effective as and less toxic than conventional amphotericin B. Therapy is continued for a total of 10 to 12 weeks. Amphotericin B has also been applied topically in the orbital cavities in patients with RCM, although it is not clear whether this is beneficial.

Amphotericin B is not effective in all cases, particularly if the patient presents late in the disease course and has inoperable or disseminated disease. Mucor reacts variably to amphotericin. Sensitivity testing is not standardized and does not necessarily correlate with disease. The therapeutic activity of amphotericin B is also limited by its potentially severe side effects. Impaired renal function often leads to cessation of therapy. The liposomal preparation of amphotericin B may help to alleviate this problem and allow for higher doses of medication to be administered. Although synergism of amphotericin B and rifampin in treating zygomycosis has been suggested by some authors, this has not been demonstrated conclusively in clinical trials.

None of the currently available azoles (ketoconazole, itraconazole, fluconazole, or voriconazole) or echinocandins has a role in the treatment of mucormycosis. Mucor is highly resistant to itraconazole in vitro. A new, broad-spectrum triazole, posaconazole (not yet clinically available), has been shown to be active in a murine model of mucormycosis, although no parenteral form is available.

Currently, the role of colony-stimulating factors as adjuncts to surgical and antifungal therapy still remains unclear, beyond that of increasing the neutrophil count in patients with neutropenia.

Some case reports have suggested benefit from adding hyperbaric oxygen to standard therapy (13). Proponents suggest that oxygen-based free radicals are believed to be responsible for the fungistatic and fungicidal effects of hyperbaric oxygen, which may potentiate the antifungal effect of amphotericin B by reversing tissue hypoxia, which protects fungal protoplasts from lysis. Because of the uncontrolled nature of the observations and the absence of a rationale for treating an aerobic fungus with oxygen, this form of therapy cannot be routinely recommended at present.

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