Medication Summary
In aspergillosis, high-dose intravenous amphotericin B has traditionally been used to eradicate the underlying organism. Voriconazole has been approved as a first-line agent in the treatment of invasive aspergillosis and is available in both parenteral and oral formulations. Typically, voriconazole is used with caspofungin. 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. [23] Ungual aspergillosis patients have been successfully administered topical efinaconazole. [19]
Itraconazole, corticosteroids, posaconazole, caspofungin, terbinafine, and micafungin have also been reportedly effective in some cases of aspergillosis. Itraconazole and corticosteroids are mainly used for allergic bronchopulmonary aspergillosis (ABPA) or allergic Aspergillus sinusitis. The length of treatment varies in the literature, but treatment is likely to be most effective if prolonged. Studies show posaconazole as an alternative treatment for invasive aspergillosis in patients previously resistant to or intolerant of other antifungal therapies. [24] Combination antifungal therapies have also been used in patients with aspergillosis that is associated with a greater degree of treatment resistance.
Antifungal agents
Class Summary
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)
Amphotericin B is a polyene antibiotic produced by a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. Amphotericin B binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.
Itraconazole (Sporanox)
Itraconazole has fungistatic activity. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Voriconazole (VFEND)
Voriconazole is used for primary treatment of invasive aspergillosis and salvage treatment for infection with Fusarium species or Scedosporium apiospermum. It is a triazole antifungal that inhibits fungal CYP450–mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.
Caspofungin (Cancidas)
Caspofungin is used to treat refractory invasive aspergillosis. It is the first of a new class of antifungal drugs (glucan synthesis inhibitors). It inhibits synthesis of beta-(1,3)-D-glucan, an essential component of the fungal cell wall.
Micafungin (Mycamine)
Micafungin is a member of new class of antifungal agents, echinocandins, that inhibit cell wall synthesis. It inhibits the synthesis of 1,3-beta-D-glucan, an essential fungal cell wall component not present in mammalian cells. It is used to treat invasive aspergillosis.
Posaconazole (Noxafil)
Posaconazole is a triazole antifungal agent. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption. It is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.
It is available as an oral suspension (200 mg/5 mL), 100-mg delayed-release tablet, and injection. Posaconazole injection is administered as a loading dose of 300 mg twice on the first day of treatment, followed by 300 mg once daily thereafter. The tablets are administered as a loading dose of 300 mg twice daily on day 1, followed by a once-daily maintenance dose of 300 mg.
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Primary cutaneous aspergillosis at a site of an intravenous catheter in a boy with leukemia.
