The use of contaminated bandages and other dressings has caused cutaneous mucormycosis. Failure to examine areas under dressings or to recognize the significance of deterioration in preexisting wounds may produce severe cutaneous and, ultimately, disseminated disease. Place patients with severe prolonged neutropenia in rooms equipped with high-efficiency particulate air (HEPA) filters, when feasible. Secondary prophylaxis is often used after therapy among patients who remain immunocompromised. No prospective comparative studies of the primary treatment of mucormycosis have been performed, largely because of the rarity of this disease. In current practice, amphotericin B and isavuconazole are the two antifungal agents licensed by the US Food and Drug Administration (FDA) for the primary therapy of mucormycosis.

First-line treatment is with an amphotericin derivative, preferably the liposomal form of amphotericin B to minimize nephrotoxicity. Other options include amphotericin B deoxycholate, isavuconazole, and posaconazole. Liposomal and lipid complex amphotericin B Amphotericin B has proven efficacy in the treatment of mucormycosis. At the present time, the liposomal formulation (AmBisome) is the drug of choice based on efficacy and safety data. [,, ] Lipid preparations of amphotericin B are used at 5 mg/kg/d.

[] Some have used doses of up to 7.5-10 mg/kg/d to treat mucormycosis, especially CNS disease []. The use of higher doses, however, has been associated with rates of nephrotoxicity up to 40% without a concomitant mortality benefit. Amphotericin B Amphotericin B deoxycholate can also be used to treat mucormycosis, particularly when other formulations prove too costly. The typical dose is 1-1.5 mg/kg/d.

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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. This is of particular concern since many patients who develop mucormycosis have preexisting renal disease (eg, diabetics, transplant recipients). Monitor the renal function of patients taking amphotericin B; doubling of serum creatinine over the baseline levels is an indication for changing to liposomal amphotericin B.

The efficacy of isavuconazole in the treatment of invasive mucormycosis has not been evaluated in randomized controlled trials because of the rarity of this disease. The approval of this medication was based on a noncomparative, single-arm, open-label, matched, case-control trial (VITAL). Of 149 patients enrolled, 37 had proven (86%) or probable (14%) mucormycosis.

Sap New License Keygen. Twenty-one patients received primary treatment with ISZ, while 11 patients received ISZ salvage therapy; 5 were intolerant to other antifungals. Controls treated with amphotericin (67% liposomal, 12% lipid complex, 21% deoxycholate) were matched from the Fungiscope Registry. Cdr King Usb Tv Tuner Driver Download.

Isavuconazole- and amphotericin-treated patients had similar day-42 weighted all-cause mortality at 33% and 41%, respectively. Patients received ISZ for a median of 84 days versus 18 for amphotericin, suggesting more favorable tolerability. Isavuconazole offers several advantages over other triazoles (ie, posaconazole, voriconazole), apart from its wider spectrum of antifungal activity. The drug has excellent oral bioavailability not reliant on food intake or gastric pH and is also available in an intravenous formulation, which does not contain the nephrotoxic solubilizing agent cyclodextrin. Switching between oral and IV forms does not require dose adjustment.

ISZ displays linear and predictable pharmacokinetics with minimal CYP3A4 interactions, reducing or eliminating the need for therapeutic drug monitoring. Unlike voriconazole, ISZ does not cause phototoxicity, increased risk of squamous cell carcinoma, or visual disturbance.

The clinical significance of ISZ-related QTc shortening is unknown, but it is reasonable to avoid this medication in patients with familial short QT syndrome and to avoid co-administrating with sodium channel–blocking antiepileptics. Posaconazole can be used for off-label salvage treatment of mucormycosis in patients intolerant to amphotericin B. Issues with the absorption of the oral suspension of posaconazole, particularly decreased absorption in the setting of proton pump inhibitor (PPI) or antimotility agent (eg, metoclopramide) use have been overcome with the introduction of a delayed-release tablet formulation. [, ] An intravenous formulation is also available.

Therapeutic drug monitoring may still be considered in patients on potent CYP450 inhibitors. Several case reports have discussed the use of posaconazole, [, ] including as salvage therapy. [] A review of 96 patients treated 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).

[] 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 (see below). Most Mucorales species show moderate in vitro resistance to the echinocandins; these agents cannot be used alone in the treatment of mucormycosis. [] Animal and limited clinical data have suggested that combination therapy with amphotericin and an echinocandin may improve survival. [,,,, ] However, a recent retrospective cohort study of combination liposomal amphotericin B (L-AmB) with posaconazole, L-AmB with echinocandins, and posaconazole with echinocandins showed no differences in mortality between monotherapy and combination treatment groups. [] The in vitro combinations of isavuconazole with micafungin or amphotericin resulted in a range of interactions, some concentration-dependent, ranging from antagonism to synergy against various Mucorales. Finally, the use of iron chelators without xenosiderophore activity (eg, deferasirox) has been described in case reports.

[] Older iron chelators, namely deferoxamine, can be exploited as an iron source by Rhizopus, thereby increasing the risk of mucormycosis. [] Newer agents such as deferasirox were hypothesized to decrease the risk of mucormycosis via iron starvation; however, they have not proven clinically efficacious. [] In an immunosuppressed murine model of pulmonary mucormycosis, a combination of deferasirox with posaconazole increased the AUC/MIC of posaconazole but failed to demonstrate improved efficacy over monotherapy. [] In the DEFEAT study, 20 patients with mucormycosis were randomly assigned to L-AmB plus deferasirox or L-AmB plus placebo; the deferasirox arm had a higher 90-day mortality rate. For patients who successfully complete therapy for mucormycosis and who subsequently require immunosuppressive treatments (eg, chemotherapy in a patient with cancer), whether daily oral posaconazole or isavuconazole should be given as secondary prophylaxis against disease relapse is unknown. Evidence-based data on the best strategy for secondary prophylaxis are not currently available.

[] Owing to their broad spectrum of anti-mold activity, safety, tolerability and oral bioavailability, there is considerable potential for inappropriate empiric and prophylactic use of the newer triazole antifungals. Specialty Editor Board Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Received salary from Medscape for employment. For: Medscape. John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance John L Brusch, MD, FACP is a member of the following medical societies:, Disclosure: Nothing to disclose.