Fungal infections are on the rise as the number of patients with compromised immune systems continues to increase. The need for safer and more effective antifungals has resulted in the search for novel
drug classes and for modifications to existing classes, with the aim of enhancing their antifungal spectra and potency. In this review, two classes of antifungals are discussed: the pradimicin-
benanomicin antibiotics and the newer
triazole derivatives. These have activity against Candida spp., Cryptococcus neoformans and Aspergillus spp., as well as variable activity against other less commonly encountered fungi including Pneumocystis carinii.
Pradimicins-
benanomicins are generally fungicidal, whereas the newer
azoles appear to be selectively fungicidal to Cryptococcus neoformans and Aspergillus spp. Pradimicin-benanomicin acts by binding to
mannan and alters membrane integrity. One water-soluble pradimicin candidate,
BMS-181184, has been selected for clinical development. The
triazoles act by inhibiting
cytochrome P450 sterol 14a-demethylase. Four
triazoles either currently in clinical development (
voriconazole and
D0870) or being considered as clinical candidates (
ER-30346 and
Sch 56592) will be discussed. The antifungal spectra, pharmacokinetic and toxicologic data in animals, and efficacy results in experimental
infection models will be reviewed for
BMS-181184 and the four newer
triazoles. Results from the early clinical trials for
voriconazole and
D0870 will also be discussed.