Medication Summary
Voriconazole is now the drug of choice for the treatment of invasive aspergillosis (IA). Although disease outcomes substantially improve with antifungal treatment, patient survival and infection resolution depend on improved immunosuppression. Response rates are low if the patient remains neutropenic. Voriconazole has shown a good outcome in 34% of patients with cerebral aspergillosis, which was previously associated with a high mortality. Caspofungin is an echinocandin that is primarily used as a salvage drug either alone or in combination with amphotericin B lipid preparations.
Amphotericin B has a broad antifungal spectrum but has limited use in view of significant nephrotoxicity and dose-limiting side effects. Various amphotericin B lipid preparations are available to help reduce nephrotoxicity. Lipid preparations of amphotericin B (ABLC, Abelcet) are approved by the FDA to treat invasive fungal infections in patients who are intolerant or refractory to conventional amphotericin (ie, deoxycholate). Amphotericin B cholesteryl sulfate complex (Amphotec) and the liposomal formulation of amphotericin B (AmBisome) have received FDA approval for the treatment of invasive aspergillosis in patients who cannot tolerate or who fail to respond to conventional amphotericin B deoxycholate. These lipid formulations are picked up preferentially by the reticuloendothelial system and are broken down by lipases locally at the site of infection. [19]
Caspofungin and voriconazole combinations have also shown to be successful as salvage drug therapy for invasive aspergillosis. Posaconazole is a new triazole that was recently approved by the FDA. Itraconazole has a status of a prophylaxis drug and is used in neutropenic patients in several centers. Steroid administration is the mainstay treatment for allergic bronchopulmonary aspergillosis (ABPA).
Antifungal agents
Class Summary
The mechanism of action in these agents may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.
The azole group of drugs, including voriconazole, inhibit the cytochrome P450 (CYP)-dependent enzyme, 14-a-demethylase, which leads to the accumulation of toxic sterol precursors. Echinocandins (eg, caspofungin) inhibit synthesis of beta-(1,3)-D-glucan, an essential component of fungal cell wall.
Voriconazole (VFEND)
Used for primary treatment of invasive aspergillosis and salvage treatment of Fusarium species or Scedosporium apiospermum infections. A triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis.
Amphotericin B (Amphocin, Fungizone)
Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols in the fungal cell membrane, such as ergosterol, causing intracellular components to leak and the subsequent death of fungal cell.
Amphotericin B lipid complex (Abelcet) - - Amphotericin B liposome (AmBisome)
FDA approved to treat invasive fungal infections in patients who are intolerant to or refractory to conventional amphotericin therapy.
Itraconazole (Sporanox)
Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450–dependent synthesis of ergosterol. Used alone as an alternative treatment for nonmeningeal cases and for patients who are intolerant of or whose infections are refractory to amphotericin B therapy.
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.
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 PO susp (200 mg/5 mL). Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk due to severe immunosuppression.
Corticosteroids
Class Summary
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. These agents also modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Meticorten, Sterapred)
Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
