Which medications in the drug class Antifungals are used in the treatment of Coccidioidomycosis and Valley Fever?

Updated: Aug 27, 2019
  • Author: Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH; Chief Editor: Michael Stuart Bronze, MD  more...
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Antifungal agents preferentially bind to the primary fungal cell membrane sterol (ergosterol). Amphotericin B increases the permeability of the cell membrane, which in turn causes intracellular components to leak. Azoles interfere with an enzyme in the sterol biosynthesis pathway production of cell membrane ergosterol. Echinocandins block fungal cell wall synthesis by inhibiting 1,3-beta glucan synthase.

Amphotericin B

Amphotericin B is the drug of choice for rapidly progressing coccidioidal infection and disease nonresponsive to oral azole therapy. It is administered IV or intrathecally. Intrathecal amphotericin B has been used for coccidioidal meningitis.

Amphotericin B is a polyene antifungal agent produced by a strain of Streptomyces nodosus. Depending on the concentration attained in body fluids and on fungal susceptibility, this agent can be fungistatic or fungicidal. It binds to sterols (eg, ergosterol) in the fungal cell membrane, causing intracellular components to leak, with subsequent cell death. Metabolic clearance is prolonged and not affected by renal or hepatic insufficiency.

Three lipid formulations (Ambisome, Abelcet, Amphotec) promising for reducing toxicity are currently licensed for use when amphotericin B fails or is unacceptably toxic. There is a significant reduction in nephrotoxicity and infusion-related reactions with continuous 24-h infusion vs conventional 2-h to 6-h infusion.

Fluconazole (Diflucan)

Fluconazole is a synthetic triazole antifungal (broad-spectrum bistriazole) that selectively inhibits fungal CYP450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol. It is used to treat mild-to-moderate infections or severe or life-threatening infections in patients intolerant of amphotericin B. It may be used for maintenance after course of amphotericin B in coccidioidal meningitis. It penetrates CSF well. Metabolic clearance is prolonged in renal dysfunction.

Fluconazole is preferred over ketoconazole because of better response rates and less GI and endocrine adverse effects. It is available as an oral suspension.


Ketoconazole is an imidazole broad-spectrum antifungal agent that inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

This agent has been used in treatment of coccidioidomycosis, although fluconazole and itraconazole are preferred because of low response rates (< 40%) with ketoconazole. In addition, it may have greater GI and endocrine adverse effects at high doses.

Administer ketoconazole orally for mild-to-moderate infections that warrant treatment. It penetrates CSF poorly, but in unusual cases is used to treat coccidioidal meningitis.

Itraconazole (Sporanox)

A triazole analogue of ketoconazole, itraconazole is preferred to its parent compound because of enhanced safety and efficacy. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP450-dependent synthesis of ergosterol, a vital component of fungal cell membranes. It is used for mild-to-moderate infections that warrant treatment. Despite poor CSF penetration, it is successfully used to treat coccidioidal meningitis.

An IV form is available, but long-term usage is not established. Itraconazole is also available in an oral solution, which provides better, more consistent absorption than the capsule. Take capsules with full meal to improve absorption, but take oral solution on empty stomach, if possible.

Voriconazole (Vfend)

Voriconazole is a triazole antifungal agent that inhibits fungal CYP450-mediated 14 alpha-lanosterol demethylation, which is essential in fungal ergosterol biosynthesis. Case reports describe efficacy in disseminated disease or meningitis refractory to first-line agents.

Posaconazole (Noxafil)

Posaconazole is a triazole antifungal agent that possesses structural similarities to itraconazole. It blocks ergosterol synthesis by inhibiting the enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. This action results in cell membrane disruption.

Posaconazole is available as an oral suspension (200 mg/5 mL). It is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk because of severe immunosuppression.

Caspofungin (Cancidas)

Caspofungin 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 fungal cell wall. It is used to treat refractory invasive aspergillosis.

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