eMedicine Specialties > Dermatology > Fungal Infections
Aspergillosis: Treatment & Medication
Updated: Nov 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
In both disseminated and limited cutaneous disease, high-dose intravenous amphotericin B has been the traditional antifungal used to eradicate the underlying organism. However, voriconazole is also approved as a first-line agent and is being used with increased frequency. Other treatment options include itraconazole and caspofungin.3,4 For Aspergillus -induced onychomycosis, treatment is with oral itraconazole because topical medications have very limited efficacy in eradicating fungus from the nail.
Surgical Care
Several case reports have documented the effectiveness of surgical excision in the treatment of primary cutaneous aspergillosis. Some of the patients also received concurrent or subsequent systemic antifungal therapy.
Consultations
- Consult a dermatologist for diagnosis, excision, and wound care.
- Consult an infectious diseases specialist for treatment recommendations in the setting of systemic disease.
Medication
High-dose intravenous amphotericin B has traditionally been used to eradicate the underlying organism. However, voriconazole has been approved as a first-line agent in the treatment of invasive aspergillosis and is available in both parenteral and oral formulations. A multicenter, randomized, open-label trial comparing the efficacy of voriconazole to amphotericin B demonstrated better response rates, improved survival, and fewer severe adverse effects in those receiving voriconazole therapy.5
Itraconazole, posaconazole, caspofungin, terbinafine, and micafungin have also been reportedly effective in some cases. The length of treatment varies in the literature, but treatment is likely to be most effective if prolonged. Recent studies show posaconazole as an alternative treatment for invasive aspergillosis in patients previously resistant to or intolerant of other antifungal therapies.6 Combination antifungal therapies have also been used in patients with disease that is associated with a greater degree of treatment resistance.
A related Medscape CME course is FDA Approvals: Viread and Cancidas.
Antifungal agents
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 (Amphocin, Fungizone)
Polyene antibiotic 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.
Adult
3-5 mg/kg/d IV of liposomal amphotericin B over 120 min; increase as tolerated
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, aminoglycosides, tacrolimus, cisplatin, and acetazolamide; in vitro and animal studies have suggested the development of fungal resistance to amphotericin B concurrently administered with imidazoles; when administered with amphotericin B, zidovudine leads to an increased risk of nephrotoxicity and hematologic toxicity via an unknown mechanism
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 electrolyte levels (eg, magnesium, potassium), liver function, CBC count, and hemoglobin concentrations; resume therapy at lowest level (eg, 0.25 mg/kg) when therapy is interrupted for >7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock
Itraconazole (Sporanox)
Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Adult
200 mg PO qd; not to exceed 400 mg/d; increase in 100-mg increments if no improvement (administer >200 mg/d in divided doses)
200 mg IV bid for 4 doses, followed by 200 mg/d
Pediatric
Not established; suggested dose 100 mg/d for systemic fungal infections
Antacids may reduce absorption; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce levels (phenytoin metabolism may be altered)
Documented hypersensitivity; breastfeeding
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
Caution in hepatic insufficiencies
Voriconazole (VFEND)
Used for primary treatment of invasive aspergillosis and salvage treatment for infection with Fusarium species or Scedosporium apiospermum. A triazole antifungal that inhibits fungal CYP450–mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.
Adult
Loading dose: 6 mg/kg IV q12h infused over 2 h for 2 doses
Maintenance: 4 mg/kg IV q12h infused over 2 h; when able to tolerate PO, may switch to 200 mg PO q12h (administer PO 1 h ac or pc)
Note: For inadequate response, may increase to 300 mg PO q12h; <40 kg administer oral maintenance dose of 100 mg PO q12h (may increase to 150 mg PO q12h)
Pediatric
<12 years: Not established
>12 years: Data limited; administer as in adults
CYP450 2C19 (highest affinity), CYP2C9, and CYP3A4 (minor) substrate and inhibitor; CYP450 inducers (eg, rifampin) have shown to decrease steady state peak plasma levels by as much as 93%; may increase serum levels of drugs metabolized by CYP450 2C19 or CYP2C9, of which some are contraindicated (eg, sirolimus, pimozide, quinidine, cisapride, ergot alkaloids), others may need more frequent monitoring (eg, cyclosporine, tacrolimus, warfarin, HMG-CoA inhibitors, benzodiazepines, calcium channel blockers)
Documented hypersensitivity; do not administer IV form with CrCl <50 mL/min (decreased excretion of IV vehicle); coadministration with rifampin, rifabutin, carbamazepine, barbiturates, sirolimus, pimozide, quinidine, cisapride, or ergot alkaloids
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Decrease maintenance dose with hepatic dysfunction; common adverse effects include visual disturbances, fever, rash (including Stevens-Johnson syndrome and phototoxicity), vomiting, nausea, diarrhea, headache, sepsis, peripheral edema, abdominal pain, and respiratory disorder; rare cases of severe hepatotoxicity have been reported
Caspofungin (Cancidas)
Used to treat refractory invasive aspergillosis. First of a new class of antifungal drugs (glucan synthesis inhibitors). Inhibits synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall.
Adult
70 mg IV over 1 h on day 1; 50 mg IV qd thereafter
Pediatric
Not established
Coadministration with cyclosporine may increase risk of hepatotoxicity; carbamazepine, nelfinavir, efavirenz, or dexamethasone may decrease levels; may decrease levels of tacrolimus; rifampin decreases caspofungin levels by 30% (ie, adjust dose to 70 mg/d)
Documented hypersensitivity
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
Caution in moderate hepatic dysfunction (ie, decrease dose to 35 mg/d); may exacerbate preexisting renal dysfunction or myelosuppression
Antifungal Agent, Systemic
Micafungin (Mycamine)
Member of new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. Inhibits synthesis of 1,3-beta-D-glucan, an essential fungal cell wall component not present in mammalian cells.
Adult
Dosages vary
Pediatric
Not established
Increases sirolimus and nifedipine AUC approximately 20%
Documented hypersensitivity
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 may include headache, nausea, vomiting, and abdominal pain; other adverse effects include rash, delirium, phlebitis, shock, leukopenia, and hyperbilirubinemia; rare cases of elevated hepatic enzyme, BUN, and creatine levels have been reported; transient acute intravascular hemolysis and hemoglobinuria may occur; do not mix or infuse in same IV line with other medications because precipitate forms with other commonly used medications (flush existing IV line with 0.9% sodium chloride solution before and after infusion); protect from light following dilution
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 infections in patients at high risk because of severe immunosuppression.
Adult
200 mg (5 mL) PO tid with food or liquid nutritional supplement to enhance absorption
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 Aspergillosis |
| Overview: Aspergillosis |
| Differential Diagnoses & Workup: Aspergillosis |
 Treatment & Medication: Aspergillosis |
| Follow-up: Aspergillosis |
| Multimedia: Aspergillosis |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
Keywords
cutaneous aspergillosis, fungal infection, Aspergillus fumigatus, A fumigatus, Aspergillus flavus, A flavus, Aspergillus terreus, A terreus, Aspergillus chevalieri, A chevalieri, Aspergillus niger, A niger, Aspergillus ustus, A ustus
