Echinocandins

Agents: caspofungin, micafungin,  anidulafungin

The echinocandins are the latest class of antifungal agents to be introduced in clinical practice and are slowly changing the way some fungal diseases are treated. They work by inhibiting the synthesis of beta-1,3-glucan, a component of the fungal cell wall. This mechanism of action is distinct from that of other antifungals and gives clinicians a new area of fungi to target. The three available echinocandins are similar drugs with virtually indistinguishable spectra. They are very well tolerated and have excellent activity against Candida, but they all suffer from the same pharmacokinetic setback: lack of an oral formulation. They have considerably fewer drug interactions than azoles, are safer than polyenes, and have great activity against fluconazole-resistant yeasts.

Spectrum

Good: Candida albicans, Candida glabrata, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Candida krusei, Aspergillus species

Moderate: Candida parapsilosis, some dimorphic fungi

Poor: Zygomycetes and most non-Aspergillus moulds, Cryptococcus neoformans

Adverse Effects

Echinocandins have an excellent safety profile.  They can cause mild histamine-mediated infusion-related reactions, but these are not common and can be ameliorated by slowing the infusion rate.  Hepatotoxicity is also possible with any of these agents, but this is not common.

Important Facts

• Differences among the echinocandins are minor and mostly pharmacokinetic. Caspofungin and micafungin are eliminated hepatically by non– cytochrome P450 metabolism, while anidulafungin degrades in the plasma and avoids hepatic metabolism. Despite this unique method of elimination, it is not completely devoid of hepatotoxicity.

• Echinocandins have excellent fungicidal activity against  Candida, but against  Aspergillus species they exhibit activity that is neither classically cidal nor static. Instead, they cause aberrant, nonfunctional hyphae to be formed by the actively growing mould.

• All of the echinocandins are less active against Candida parapsilosis than the other common clinical species. It has yet to be determined whether this is likely to result in clinical failure, because this organism has been success-fully treated with these drugs. If your patient is infected with this organism, be sure to change any IV catheters your patient has and consider fluconazole therapy instead.

• Though drug interactions with the echinocandins are minor, there are some of which you should be aware, particularly with caspofungin and micafungin. Be careful when you use them with the immunosuppressants cyclosporine  (caspofungin) and sirolimus (micafungin).

What They’re Good For

Echinocandins are becoming drugs of choice for invasive candidiasis, particularly in patients who are clinically unstable. They are also useful in the treatment of invasive aspergillosis but do not have the level of supporting data that voriconazole and the polyenes do for this indication. All of them are used for esophageal candidiasis, and some are used in prophylaxis or empiric therapy of fungal infections in neutropenic patients.

Don’t Forget!

Echinocandins are great drugs for invasive candidiasis, but they are not cheap. After beginning empiric therapy with an echinocandin, transition your patient to fluconazole if he or she has a susceptible strain of Candida and no contraindication to fluconazole.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.

مواضيع ذات صلة

Antifungal Chemotherapy

Pimaricin

Posaconazole

Voriconazole

Itraconazole

Fluconazole

Introduction to Azoles

Antimetabolites

Polyenes

Introduction to Antifungal Drugs