Which medications in the drug class Antifungal Agents are used in the treatment of Pediatric Severe Combined Immunodeficiency?

Updated: Apr 28, 2021
  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Harumi Jyonouchi, MD  more...
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Answer

Antifungal Agents

Mucocutaneous candidiasis usually can be treated with fluconazole. Invasive Candida, Aspergillus, and other fungal infections require IV amphotericin B. Prevention of Aspergillus infection and treatment of certain Candida infections that are resistant to fluconazole may be accomplished effectively with itraconazole.

Fluconazole (Diflucan)

Fluconazole has fungistatic activity. It is a synthetic oral antifungal (a broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.

A loading dose is given on day 1, followed by maintenance at 50% of the loading dose. Fluconazole may be administered either IV orally with similar efficacy. Length of treatment is a minimum of 10 days; longer courses are determined individually, with other risk factors (eg, ongoing broad-spectrum antibiotic therapy) taken into account.

Itraconazole (Sporanox)

Itraconazole is used most commonly to prevent Aspergillus infection. An oral solution, 10 mg/mL, is administered on an empty stomach; capsules, 100 mg, are taken with food.

Amphotericin B deoxycholate (amphotericin B conventional)

A test dose of 0.1 mg/kg is recommended by the manufacturer but is often omitted. Infusion of the total dose over 2-4 hours has been recommended, but infusion over 1 hour seems to be adequate. Because of the high incidence of toxicity, renal, hepatic, electrolyte, and hematologic status must be monitored closely. In particular, potassium and magnesium levels usually are monitored daily. Salt loading with 10-15 mL/kg of normal saline before each dose is used to decrease the risk of nephrotoxicity.

Premedication with acetaminophen and diphenhydramine 30 min before and 4 hours after infusion decreases the typical adverse effects of fever, chills, hypotension, nausea, and vomiting. Hydrocortisone may be admixed to the IV solution (1 mg to 1 mg of amphotericin, not to exceed 25 mg).

The 3 lipid amphotericin products are amphotericin B lipid complex (Abelcet), amphotericin B cholesteryl sulfate (Amphotec), and amphotericin B liposomal (AmBisome). Lipid amphotericin B is used when toxicity from nonlipid amphotericin B is unacceptable. In some patients, lipid products seem to cause less fever, gastrointestinal irritation, chills, and headache. It is unclear whether their renal toxicity is lower.

Amphotericin B lipid complex (ABLC, Abelcet)

This agent is amphotericin B in phospholipid complexed form; it is a polyene antibiotic with poor oral availability. Amphotericin B is produced by a strain of Streptomyces nodosus; it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.

Amphotericin B, liposomal (AmBisome)

This is a lipid preparation consisting of amphotericin B within unilamellar liposomes. It delivers higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity.

Amphotericin B is a polyene antibiotic with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.

Amphotericin B colloidal dispersion (Amphotec)

Amphotericin B colloidal dispersion is a lipid preparation consisting of amphotericin B attached to lipid discoid structures. Amphotericin B is a polyene antibiotic with poor oral availability. It is produced by a strain of Streptomyces nodosus, and it can be fungistatic or fungicidal. The drug binds to sterols (eg, ergosterol) in the fungal cell membrane, causing leakage of intracellular components and fungal cell death. Toxicity to human cells may occur via this same mechanism.


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