cilofungin and Mycoses

For more than two decades, amphotericin B has been the single broad-spectrum agent for the treatment of systemic mycoses. Amphotericin B is not always effective, must be given parenterally, and is associated with a host of adverse reactions. Despite amphotericin B toxicity, until recently the systemic mycoses did not rate enough attention to prompt a search for new alternatives. However, three recent events have overcome this inertia: the gradually increasing use of potent immunosuppressive agents and broad-spectrum antibacterial drugs; the discovery of the relatively nontoxic azole classes of antifungal drugs in the 1980s and the rapid emergence of AIDS, with its severe accompanying opportunistic fungal infections. In just ten years we have seen the emergence of second-generation imidazole and third-generation triazole antifungal drugs and, most recently, entirely new classes of agents. It is remarkable that so many alternatives are becoming available just at the time when new antifungal drugs have become a major need. This discussion will concentrate on the new antifungal drugs of the past ten years, with the exception of developments in the polyenes and flucytosine, which are covered elsewhere.

Topics: Aminoglycosides; Anti-Bacterial Agents; Antifungal Agents; Azoles; Echinocandins; Fluconazole; Fungi; Humans; Itraconazole; Ketoconazole; Mycoses; Peptides; Peptides, Cyclic; Triazoles

The multiplication of iatrogenic factors, nosocomial diseases and acquired immunodeficiency syndrome is responsible for an ever increasing number of deep opportunistic mycoses, namely candidiasis, aspergillosis and cryptococcosis. The advent of a wide variety of rare opportunistic fungi is a fairly recent and worrying phenomenon. To combat these infections, often very serious, our therapeutic armentarium is rather scanty. Moreover, the prescription of the available drugs is limited by their toxicity, their spectrum and their route of administration or by the emergence under treatment of resistant mutants. Beside old products, such as amphotericin B and 5-fluorocytosine, miconazole and, mainly ketoconazole (both azole derivatives) were the first steps towards oral administration and low toxicity. Fluconazole is a triazole antifungal compound with a very original distribution to the meninges and urinary tract; it is mainly used in candidiasis and cryptococcosis. Another triazole compound, itraconazole, presents the particularity of being active against Aspergillus spp., Cryptococcus spp. and some agents of exotic mycoses. These two products are well tolerated and should soon be available for use in deep visceral mycoses. Other azole derivatives are under study. Among compounds issued from new chemical families, terbinafine (allylamine) is particularly active against dermatophytes, and cilofungine (a polypeptide) against fungi. These drugs are in the experimental stage. Research should be pursued aimed at developing, probably in new chemical families, and agent that is fungicidal in vivo.

Topics: Allylamine; Amphotericin B; Antifungal Agents; Echinocandins; Fluconazole; Flucytosine; Humans; Itraconazole; Ketoconazole; Miconazole; Mycoses; Naphthalenes; Peptides; Peptides, Cyclic; Terbinafine

Cilofungin (LY121019) is a new lipopeptide antifungal drug. We tested this drug against 141 pathogenic fungal isolates. All fungal species were tested by broth dilution at 35 degrees C. Malassezia furfur was tested by agar dilution. The results demonstrate the specificity of cilofungin activity. Candida albicans, Candida tropicalis, and Malassezia pachydermatis were highly susceptible, whereas Candida parapsilosis, Candida pseudotropicalis, Candida krusei, Torulopsis glabrata, Blastomyces dermatitidis, Cryptococcus neoformans, Aspergillus species, M. furfur, and Paracoccidioides brasiliensis were more resistant.

Topics: Antifungal Agents; Echinocandins; Evaluation Studies as Topic; Fungi; Humans; Microbial Sensitivity Tests; Mycoses; Peptides; Peptides, Cyclic