According to Dr. Rosen, the candins are strong medicine for “seriously sick patients with really bad bugs.” Basically, the candins make it impossible for the fungi to build their cell walls, and the current trend among fungal infection specialists is to combine an echinocandin with one of the new triazoles.
He noted that he has worked with caspofungin (Cancidas) quite a bit and has found that it greatly extends Candida coverage. In HIV-positive patients, it can clear refractory esophageal candidiasis very quickly.
Micafungin (Mycamine) is the other hot candin these days. It is excellent for Candida and Aspergillus, though it does not work as well against Zygomycetes or Fusarium.
The main drawback to the candins as a class is that they are available only in intravenous forms. “All these drugs are cyclic hexapeptides, and all are destroyed by acids. Therefore, oral formulations are not possible,” Dr. Rosen said.
There are a few other antifungals in the offing. PLD-118, also known as icofungipen, is neither an azole nor a candin. It is a tiny molecule that binds to fungal isoleucyl transfer RNA, thus affecting a wide range of Candida species. PLD-118 is being developed as topical as well as systemic therapy.
Milbemycin, derived from Streptomyces, trips up the fungal gene that enables resistant fungi to “spit out” other antifungals, he said. When it eventually comes to market, it will probably find its place as an adjunct for many of the more conventional antifungals, potentiating their effects against resistant pathogens.
Finally, there's the yet-to-be properly named P-113, the world's first “swish and spit” antifungal. This drug, which is being developed as a therapeutic mouthwash, is a 12-amino acid fragment of histatin 5, a compound produced by the body that has fungistatic effects, especially against Candida. Histatin 5 is “basically what prevents most of us from getting thrush. So this drug is essentially a duplication of the natural mechanism for controlling yeasts,” Dr. Rosen said.