ABSTRACT
The systemic mycoses and especially those fungi that cause opportunistic infections, such as Candida albicans and Aspergillusfumigatus, pose important problems for the clinican who must choose from a short-list of antifungals to achieve cure. Why are there only a few choices of drugs to use and what other problems surface in treating these infections? First, as both the fungus and host are eukaryotic, the number of compounds specifically toxic for the fungus is small. Second, amphotericin-B, the "gold standard" of antifungals for the treatment of the systemic mycoses, invariably causes some degree of toxicity because it also binds to similar targets of host cells. Third, successful cure is, in part, often compromised by the low sensitivity of existing detection methods, especially in the case of invasive aspergillosis where laboratory diagnosis by blood culture most often fails [I]. Fourth, resistance to fluconazole, the azole which is commonly used to treat several mycoses, is encountered with increasing frequency. For example, pathogens such as A. fumigatus are resistant to fluconazole, so that again, there are few choices other than amphotericin B in treating invasive infections caused by this organism [I]. In the case of C. albicans, resistance to fluconazole has been reported in greater frequency, and the emergence of non-albicans Candida spp. has become a major problem in a number of clinical settings because of the inherent resistance of these species to fluconazole. Thus, the answers to the questions raised above are fairly straightforward, but solutions are not at hand. Nevertheless, in spite of these problems in treatment, drugs which target ergosterol (amphotericin-B/azoles) of the human pathogenic fungi remain the logical choices for treatment.
