eMedicine Specialties > Infectious Diseases > Fungal Infections
Mucormycosis: Treatment & Medication
Updated: Jul 1, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Correction of the underlying abnormality and prompt institution of amphotericin B therapy and surgical resection are critical.
- Diabetic ketoacidosis requires insulin, correction of acidosis with sodium bicarbonate, and rehydration.
- Neutropenia in association with hematological malignancy and its treatment should be reversed, if possible, with the use of colony-stimulating factors and the withdrawal of cytotoxic chemotherapy.
- Wean glucocorticosteroids and other immunosuppressive drugs.
- Interrupt deferoxamine therapy. Hydroxypyridine chelators may be substituted for deferoxamine.
Surgical Care
Debridement of necrotic tissue in combination with medical therapy is mandatory for survival.
- In rhinocerebral disease, surgical care includes drainage of the sinuses and may require excision of the orbital contents and involved brain. Repeated surgery may be required, especially for rhinocerebral mucormycosis.
- Excise pulmonary lesions if they are localized to a single lobe.
- Excise cutaneous lesions entirely.
- Resect any GI masses.
Consultations
- Infectious diseases consultation - For management of antifungal therapy and coordination of medical care
- Surgical specialties consultations depending on location of disease
- Ear, nose, and throat consultation and neurosurgery consultation for rhinocerebral mucormycosis
- Thoracic surgery consultation for pulmonary involvement
- GI surgery consultation for GI involvement
- Plastic surgery consultation for cutaneous involvement
- Endocrinology consultation - For the management of unstable diabetes
- Hemato-oncology consultation - For the management of issues related to hematology and solid tumors
- Surgical ICU consultation - For supportive care
Medication
Antifungal treatment consists of amphotericin B, lipid formulations of amphotericin, or posaconazole. Although most clinical experience has focused on amphotericin agents, data on the efficacy of posaconazole are promising. This may eventually become the drug of choice, but more evaluation is needed.
Amphotericin agents
Amphotericin B has proven efficacy in the treatment of mucormycosis. Amphotericin B 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. Lipid formulations of amphotericin B allow for very high doses to be administered while better protecting renal function. Whether lipid formulations of amphotericin B provide better therapeutic outcomes is not clear, and the high cost necessitates careful consideration of use.
Renal impairment and failed treatment with conventional amphotericin B are appropriate indications for the use of the lipid formulations. Lipid preparations of amphotericin B are used at 5 mg/kg/d. Some have doses of up to 15 mg/kg/d to treat mucormycosis.
Posaconazole, a new triazole, has recently been approved by the US Food and Drug Administration (FDA). Posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression. Posaconazole 400 mg twice daily is the typical dose used in the treatment of mucormycosis.
Studies have reported that posaconazole yielded a 50-70% success rate, while the comparator (typically amphotericin B or lipid-based amphotericin, in many cases used as salvage therapy) yielded a success rate of only 25%, suggesting that posaconazole may become the preferred drug for mucormycosis. However, further studies are needed.7,8
Posaconazole has also been studied in several case reports,6 including as salvage therapy after failure of amphotericin.9 Rickerts et al (2006) reported that liposomal amphotericin B plus posaconazole was successful in the treatment of disseminated mucormycosis in a patient who could not undergo surgery.10
Other medications
Other azoles (eg, fluconazole, voriconazole) and the echinocandins 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.11,12
Antifungals
These 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.
Amphotericin B (Fungizone)
DOC produced by a strain of Streptomyces nodosus. Can be fungistatic or fungicidal. Binds to sterols (eg, ergosterol) in fungal cell membrane, causing intracellular components to leak, with subsequent fungal cell death. Active against Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, Candida species, and Aspergillus species.
Adult
1-1.5 mg/kg IV qd infused in 5% dextrose over 4-6 h
Pediatric
Administer as in adults
Antineoplastic agents may enhance the potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; risk of renal toxicity is increased with cisplatin, pentamidine, and cyclosporine
Documented hypersensitivity; renal impairment
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who are neutropenic and receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); signs of infusion-related toxicity include fever, headache, hypotension, and phlebitis; normocytic and/or normochromic anemia may develop
Liposomal amphotericin B (AmBisome)
Amphotericin B encapsulated in bilayer of liposomes. Antifungal agent of second choice when renal toxicity develops or conventional amphotericin B therapy is failing. Nephrotoxicity and infusion-related toxicity are reduced compared with conventional amphotericin B.
Adult
5 mg/kg/d IV
Pediatric
Administer as in adults
Antineoplastic agents may enhance the potential for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who are neutropenic and receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)
Amphotericin B lipid complex (Abelcet)
Amphotericin B in phospholipid complexed form. Drug of third choice when conventional amphotericin B therapy is failing, but renal function is not impaired.
Adult
5 mg/kg/d IV
Pediatric
Administer as in adults
Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Infusion-related adverse effects are common and may require pretreatment with acetaminophen, diphenhydramine, and hydrocortisone; dose-limiting renal toxicity limits use; monitor renal function, serum electrolytes (eg, magnesium, potassium), liver function, CBC, and hemoglobin concentrations; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients who are neutropenic and receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion)
Posaconazole (Noxafil)
Triazole antifungal agent. Blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression. Has also been used for serious fungal infections (eg, invasive aspergillosis, Fusarium infection, Scedosporium apiospermum infection, candidemia, candidiasis).
Adult
Treatment of serious fungal infection: 800 mg/d (in 2 or 4 divided doses) with food or nutritional supplement
Pediatric
<13 years: Not established
>13 years: Administer as in adults
Metabolized via UDP glucuronidation; P-gp efflux substrate; CYP3A4 inhibitor
UDP-G inducers (eg, rifabutin, phenytoin) and drugs that increase gastric pH (eg, cimetidine) decrease serum levels (avoid concomitant use unless benefit outweighs risk)
Inhibits CYP3A4 and may elevate serum levels of cyclosporine, tacrolimus, sirolimus, rifabutin, midazolam, phenytoin, calcium channel blockers (eg, nifedipine, bepridil), HMG-CoA reductase inhibitors (eg, lovastatin, pravastatin), ergot alkaloids, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine, or vinca alkaloids (eg, vincristine, vinblastine)
Documented hypersensitivity; coadministration with ergot alkaloids; coadministration with CYP3A4 substrates likely to result in serious toxicities (eg, terfenadine, astemizole, cisapride, pimozide, halofantrine, quinidine)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Common adverse effects include nausea, vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and elevated liver enzyme levels; closely monitor patients with severe diarrhea or vomiting for breakthrough fungal infections; rare adverse events include arrhythmias caused by QTc prolongation, bilirubinemia, or liver function impairment; caution with preexisting cardiac risk factors (eg, history of arrhythmia, hypokalemia, hypomagnesemia); food improves absorption and provides optimal serum concentration; shake well before use; administer with measuring spoon provided in package; avoid if breastfeeding
More on Mucormycosis |
| Overview: Mucormycosis |
| Differential Diagnoses & Workup: Mucormycosis |
 Treatment & Medication: Mucormycosis |
| Follow-up: Mucormycosis |
| Multimedia: Mucormycosis |
| References |
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References
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Further Reading
Keywords
Rhizopus species, mucormycosis, zygomycosis, phycomycosis, Mucorales, Rhizopus mucormycosis , Rhizomucor mucormycosis , Cunninghamella mucormycosis , Apophysomyces mucormycosis , Saksenaea mucormycosis , Absidia mucormycosis , Mucor mucormycosis , Syncephalastrum mucormycosis , Cokeromyces mucormycosis , Mortierella mucormycosis, conidiobolomycosis, entomophthoramycosis, basidiobolomycosis, pulmonary mucormycosis, rhinocerebral mucormycosis, cutaneous mucormycosis, gastrointestinal mucormycosis, disseminated mucormycosis
