Amphotericin B: A Commentary on Its Role as an Antifungal Agent and as a Comparative Agent in Clinical Trials

Since the discovery of amphotericin B and its subsequent introduction to the pharmaceutical market in the 1950s, treatment with this agent has been the standard to which all therapy for systemic fungal infection has been compared [1]. The subsequent introduction of clotrimazole, miconazole, and ketoconazole demonstrated the potential of the azole agents to supplant amphotericin B in at least a few of the diseases in which its use is indicated [2]. The potential importance of flucytosine was diminished by the relatively rapid development of resistance to the agent and by its toxicities. Fluconazole has been the only serious competitor to amphotericin B; because of its oral absorption, availability as a parenteral agent, CNS penetration, and relative lack of toxicity, it is being seriously considered as a potential agent of choice for selected cases of cryptococcal meningitis, disseminated candidiasis, and certain forms of coccidioidomycosis [2]. The subsequent introduction of itraconazole has provided an agent with excellent potential in the treatment of several of the endemic mycoses [3]. The availability of these products with their newly approved clinical indications has led many physicians to ask where amphotericin B now stands as the gold standard antifungal agent. This paper will examine the current state of the art in antifungal therapy and give recommendations with regard to the conduct of future clinical trials using this group of agents; it specifically addresses the role of amphotericin B as a comparative agent in these trials.