|
Conor Jamieson is antibiotic pharmacist, Sandwell
and West Birmingham NHS Trust. |
Sue Ford/SPL
Serious skin reactions, including Stevens-Johnson
syndrome, are among the rare side-effects of the antifungal drug
terbinafine |
SUMMARY
Fungi are eukaryotic organisms, and as such resemble mammalian cells
more than bacteria. Many effective antifungal drugs target the fungal
cell membrane and sterol biosynthesis. The fungal cell membrane has many
similarities to the mammalian cell membrane, which may account for the
toxicity seen with certain antifungal drugs.
The incidence of fungal infections has increased in the past 20–30
years, mainly due to the increased number of immunocompromised patients.
This has arisen because of the spread of HIV infection, the increasing
intensity of anticancer chemotherapy, advances in medical practice leading
to haemopoietic stem cell transplantation and more organ transplants,
increasingly invasive medical procedures such as surgery, vascular catheters,
parenteral nutrition and haemodialysis and peritoneal dialysis.
For a number of years, antifungal therapy was limited to the systemically
active azoles such as fluconazole, imidazole and ketoconazole and the
broad-spectrum but toxic antifungal drug amphotericin B. More recently,
reformulation of amphotericin B into liposomal delivery systems has resulted
in an improved safety profile for the drug. In addition, since the turn
of the century, a new azole antifungal, voriconazole, and a new class
of antifungals, the echinocandins, have been launched (of which caspofungin
is available in the UK), offering a greater choice of treatment, and
reduced toxicity compared with conventional amphotericin B. Several new
antifungal targets have also been identified, and thus a number of new
drugs are currently in development. The pace of developments in this
field means that it is important for pharmacists to have a good understanding
of the antifungal drugs currently in use.
There are a number of antifungal drugs which are too toxic or otherwise
unsuitable for systemic administration, but which are used to treat fungal
infections of the skin and mucous membranes. Panel 1 (below) outlines
the topical treatment of these infections. The remainder of this article
will focus on systemically active antifungal drugs.
Panel 1: Topical treatment of fungal infections
Candidal infections Candidal infections of the skin
can be treated with topical
imidazoles (such as clotrimazole, econazole, ketoconazole, miconazole
or sulconazole), topical terbinafine or nystatin. Nystatin is not
absorbed from the gut after oral administration and can be used to
treat intestinal candidiasis. Oral candidiasis can be treated with
nystatin pastilles or suspension. Candidal infections that are not
responsive to topical therapy will require a systemically active
azole such as fluconazole.
Dermatophyte infections Dermatophyte infections of
the skin can be treated with a topical imidazole antifungal such
as clotrimazole
or miconazole (available as creams) or by using a shampoo containing
ketoconazole, for example. Nystatin is not effective for
dermatophytosis.
Pityriasis versicolor Pityriasis versicolor
(a superficial infection caused by the yeasts of the Malassezia species,
see p314 (PDF 90K)) can be
treated with topical imidazoles but, since large quantities of cream
are often required, it is more convenient to use an antifungal shampoo
such as one containing ketoconazole. This is applied once daily and
left on the skin for up to five minutes before being rinsed off.
Treatment should continue for five days. If topical therapy fails,
a systemic azole such as fluconazole can be used. This is often necessary
in
immunocompromised patients.
Nail infections Amorolfine, tioconazole and undecenoate-containing
nail lacquers, paints and creams can be used as topical therapy for
nail infections in the early stages of disease, when not more than
two nails are affected. Systemically active drugs such as griseofulvin
or terbinafine are used for more advanced infection. |
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Hospital Pharmacist