An antifungal medication is a medication used to treat fungal infections such as athlete’s foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor’s prescription or for less serious infections of the nail and skin, over the counter.

Apart from side-effects like liver-damage or affecting estrogen levels, many medicines can cause allergic reactions in some people including rashes.

There are also many drug interactions and foods which must be avoided. Patients must read in detail the enclosed data sheet(s) called a patient information leaflet (PIL) of the medicine (also see our antifungal PIL collection). For example, the azole antifungals such as ketoconazole or itraconazole can be both substrates and inhibitors of the P-glycoprotein, which (among other functions) excretes toxins and drugs into the intestines. For detailed patient information leaflets (PIL) and information on antifungal medication please visit the Aspergillus website here.

The treatment of fungal infections can broadly be described in terms of three classes of antifungal drugs. The echinocandins, the azoles and the polyenes. These are described more fully here, and a PDF describing antifungals drugs their uses and side effects can be viewed here.

A brief description of some common antifungal medication is described here.

Polyenes

Amphotericin B is often used intravenously to treat systemic fungal infections. It works by binding to a fungal cell wall component called ergosterol. Amphotericin B is probably the most broad spectrum intravenous antifungal available.  It has activity against Aspergillus,Blastomyces,Candida (all species except some isolates of Candida krusei and Candida lusitania), Coccidioides, Cryptococcus,Histoplasma, Paracoccidiodes and most of the agents of zygomycosis (Mucorales), Fusarium and other rarer fungi. It is not adequately active against Scedosporium apiospermum, Aspergillus terreus, Trichosporon spp., most of the species causing mycetoma and systemic infections due to Sporothrix schenkii. Acquired resistance to amphotericin B has been described in occasional isolates, usually after long term therapy in the context of endocarditis, but is rare. Amphotericin B can cause many side effects which in some cases can be very severe.

Echinocandins

Echinocandins are often used to treat systemic fungal infections in immune deficient patients – these drugs inhibit the synthesis of glucan which is a specific component of the fungal cell wall. They include micafungin, caspofungin and anidulafungin these are best administered by intravenous means because of poor absorption.

Caspofungin is very active against all Aspergillus species. It does not kill Aspergillus completely in the test tube. There is a very limited amount of activity against Coccidioides immitis, Blastomycesdermatitidis, Scedosporium species, Paecilomyces varioti and Histoplasma capsulata but it is likely that the activity is not sufficient for clinical use.

Triazoles

Triazoles -itraconazole, fluconazole, voriconazole and posaconazole – the mechanism of action of itraconazole is the same as the other azole antifungals: it inhibits the fungal cytochrome P450 oxidase-mediated synthesis of ergosterol.

Fluconazole is active against most Candida species, with the absolute exception of Candida krusei and partial exception of Candida glabrata and a small number of isolates of Candida albicans, Candida tropicalis, Candida parapsilosis and other rare species. It is also active against the vast majority of Cryptococcus neoformans isolates. It is active against many other yeasts including Trichosporon beigelii, Rhodotorula rubra, and the dimorphic endemic fungi including Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum and Paracoccidioides brasiliensis. It is less active than itraconazole against these dimorphic fungi. It is not active againstAspergillus or Mucorales. It is active against skin fungi such as Trichophyton.

Increasing resistance in Candida albicans in patients with AIDS has been reported. Typical rates of resistance, in Candida albicans in a general hospital are 3-6%, in Candida albicans in AIDS 10-15%, in Candida krusei 100%, in Candida glabrata ~50-70%, in Candida tropicalis 10-30% and in other Candida species less than 5%.

Itraconazole is one of the most broad spectrum antifungals available and includes activity against Aspergillus, Blastomyces Candida (all species including many fluconazole resistant isolates) Coccidioides, Cryptoccocus, Histoplasma, Paracoccidioides, Scedosporium apiospermum and Sporothrix schenkii. It is also active against all skin fungi. It is not active against Mucorales or Fusarium and a few other rare fungi. It is the best agent against black moulds, including Bipolaris, Exserohilum etc. Resistance to itraconazole is described inCandida, although less often than with fluconazole and also in Aspergillus.

Voriconazole has an extremely broad spectum. It is active against the vast majority of Candida species, Cryptococcus neoformans, all Aspergillus species, Scedosporium agiospermum, some isolates of Fusarium and a multitude of rather rare pathogens. It is not active against Mucorales species such as Mucor spp, Rhizopus spp, Rhizomucor spp, Absidia spp and others. Voriconazole has become invaluable in the treatment of invasive aspergillosis.

Posaconazole has an extremely wide spectrum of action. The fungi whose growth are inhibited by posaconazole and includeAspergillus, Candida, Coccidioides, Histoplasma, Paracoccidioides, Blastomyces, Cryptococcus, Sporothrix, various species ofMucorales (causing Zygomyetes) and numerous other black moulds such as Bipolaris and Exserohilum.  The majority of Aspergillusisolates are killed by posaconazole at clinically relevant concentrations. Acquired resistance to posaconazole does occur in Aspergillus fumigatus and Candida albicans but is otherwise rare.

Isavuconazole was approved for use in EU in December 2015 (March 2015 in the US). It has activity against most clinically important yeasts and molds, including Candida spp, Aspergillus spp, Cryptococcus neoformans, and Trichosporon spp and variable activity againstMucorales spp. It is also very active against many rare pathogens including those that cause chromoblastomycosis. A large randomized study (>500 patients) demonstrated equivalent efficacy to voriconazole in invasive aspergillosis with less toxicity.
Isavuconazole is provided as a highly water soluble pro-drug allowing a simple intravenous formulation and excellent oral bioavailability. Loading doses are required due largely to its slow elimination. Its drug interaction potential appears to be less than other azole antifungals – also beneficial.

The side effects of azole drugs are well characterised and there are also some important drug-drug interactions which exclude the use of prescribing certain drugs at the same time. For a more comprehensive understanding of these issues please visit the Aspergillus Website and view individual patient information (PIL) leaflets for each drug.

New drugs

There is no doubt with increasing rates of resistance to antifungal medicines that research into effective and cost efficient antifungal drugs is a high priority. There are now numerous candidate drugs in development, several novel drug classes. See the Aspergillus Website for latest developments.