Systemic Antifungal Therapy: New Options, New Challenges

Abstract

The frequency of invasive fungal infections has increased dramatically in recent decades because of an expanding population at risk. Until now, treatment options for invasive mycoses have been primarily amphotericin B and the azoles, fluconazole and itraconazole. Traditional agents are limited by an inadequate spectrum of activity, drug resistance, toxicities, and drug-drug interactions. The recent approval of caspofungin and voriconazole clearly has expanded the number of existing antifungal drugs available. However, the enthusiasm that accompanies their availability is counterbalanced by limited clinical experience, high drug acquisition costs, and distinctive toxicities. The pharmacologic characteristics, extent of clinical experience (efficacy and toxicity), and drug acquisition costs among available systemic antifungal agents are compared, with emphasis on the new agents. Also, recommendations on the role of each agent are provided according to the most common indications for systemic antifungal therapy: invasive candidiasis, invasive aspergillosis, and febrile neutropenia.

Antifungal Activity of C-27 Steroidal Saponins

“…To our knowledge, the in vitro antifungal activity of compounds 1, 3, and 4 against C. neoformans is the most potent within the steroidal saponin class that has so far been reported, while their antifungal potency against A. fumigatus is comparable to that of diuranthoside A, a neotigogenin saponin with the same sugar moiety as in compound 3 (37). In view of limited antifungal drugs for cryptococcosis and aspergillosis (17,36), it is of particular significance for this discovery.…”

Management of Posttransplant Lung Disease

“…25 On the other hand, oral voriconazole, which is much more consistently bioavailable than itraconazole, can be continued with relative ease for an extended period of time. 26 The azole antifungal agents all competitively inhibit the hepatic excretion of cyclosporine and tacrolimus, leading to a marked increase in blood level unless there is a dosage change. In all lung recipients, it is wise to minimize exposure to construction sites, barns, caves, and other sites in nature where heavy concentrations of mold spores can be anticipated.…”

Triazole derivatives with improved in vitro antifungal activity over azole drugs

“…Major classes of antifungal compounds are currently in clinical use: polyenes, azole derivatives, allylamines, thiocarbamates, echinocandins, and fluoropyrimidines 5–8. Despite this growing list of antifungal agents, treatment of fungal diseases remains unsatisfactory.…”