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A Brief Review of Antifungal Therapy for Deep Fungal Infection

A Brief Review of Antifungal Therapy for Deep Fungal Infection

ABSTRACT: With the continuing increase in clinically important fungal disease, especially seen in the neutropenic patient, the need for new and improved systemic antifungal agents marches on. A pharmacy and therapeutics committee may select an antifungal agent based on these criteria: spectrum of action, pharmacokinetic profile, toxicity, potential for resistance, and cost. A number of agents are now available for treating deep fungal infections, including amphotericin B in conventional and liposomal formulations, and the triazoles itraconazole (Sporanox) and fluconazole (Diflucan). It is important to note that there is lack of agreement in practice over what constitutes ideal therapy. The lipid formulations of amphotericin B and the improved oral solution and new intravenous formulation of itraconazole are recent additions to therapeutic options that are already having a significant influence on drug selection and treatment practices. [ONCOLOGY 15(Suppl 9):21-25, 2001]

Several antifungal agents are now available for use
against fungal disease, including amphotericin B, itraconazole (Sporanox), and
fluconazole (Diflucan). It is important to note that there is a lack of
agreement in practice over what constitutes ideal therapy. The following
overview explains the current options along with the guidelines used at
Memorial-Sloan Kettering Cancer Center (MSKCC) in New York.

General recommendations of drugs of choice for the various fungal indications
are shown in Table 1.[1] Potential adverse reactions, contra- indications, and
drug interactions associated with these agents are shown in Table
2
.

Amphotericin B

Conventional Formulation

Amphotericin B is a potent broadspectrum agent that has been in clinical use
for 40 years.[2-6] Until the availability of itraconazole, it was the only agent
available for treating Aspergillus infection. A major drawback of conventional
amphotericin B is its toxicity profile, with renal toxicity (including acute
tubular necrosis) constituting the primary adverse effect associated with
treatment. Hypokalemia is a recurrent problem that warrants strict attention to
use of other drugs that can affect potassium balance (eg, cisplatin [Platinol],
ifosfamide [Ifex], corticosteroids, and ticarcillin/clavulanic acid [Timentin]).

Other characteristic toxicities include nausea, vomiting, and anorexia;
increased erythropoietin production; phlebitis, if the drug is administered
through a peripheral intravenous (IV) line; and (rarely) thrombocytopenia or
leukopenia. Acute reactions consist of the complex of chills, fever, tachypnea,
hypoxemia, and hypotension; premedication protocols including acetaminophen,
hydrocortisone, diphenylamine, or meperidine are helpful in alleviating these
reactions.

Lipid Formulations

The lipid formulations of amphotericin B that have become available are
associated with a degree of reduction in renal toxicity compared with the
conventional formulation.[4,5,7] However, it is far from clear whether this
reduced toxicity and improved quality of life is worth a cost that can be up to
50 times that of the standard formulation for the drug alone.

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