The development of the polyene
antibiotic,
amphotericin B, provided for the first time a
drug which was clinically effective in many serious mycotic diseases. Unfortunately, it requires parenteral administration and is often toxic, factors which limit the total cumulative dose which can be given. Efforts to utilise combinations of
amphotericin B with other agents were best realised with
amphotericin B/
flucytosine in
cryptococcal meningitis, and to a lesser degree in
systemic candidiasis. More recently, the introduction of new
imidazoles has extended the range of applications of these drugs to
fungal diseases. Two members of this group,
miconazole and
ketoconazole, are promising agents.
Miconazole is a parenterally administered agent for patients acutely ill with
candidiasis and other mycotic
infections. It may be the
drug of choice for Petriellidium boydii
infections and it is an attractive alternative to
amphotericin B for intrathecal administration to patients with
fungal meningitis.
Ketoconazole offers much less toxicity, the advantage of
oral administration, and the possibility of indefinitely prolonged
therapy. However, it does not attain high concentrations in either the urine or cerebrospinal fluid. With the
imidazoles, we have entered a new era of antifungal
therapy which may produce even better
antifungal agents than those currently available.