Continuous dosing of nikkomycin Z against systemic candidiasis, in vivo and in vitro correlates

Abstract

Candida species is the most common cause of fungemia and invasive mycoses. 1 Owing to increasing resistance of Candida albicans to some of the most commonly used treatments, and the failures of therapy in patients even when the pathogen is susceptible in vitro, 2 the search for newer drugs, particularly those with novel mechanisms of action, is ongoing. Nikkomycin Z (NIKZ) is a nucleoside peptide, originally derived from Streptomyces tendae. 3 NIKZ enters the fungal cell via peptide permeases. NIKZ is structurally similar to UDP-N-acetylglucosamine, enabling it to be a competitive inhibitor for chitin synthase enzymes, the enzymes that incorporate UDP-N-acetylglucosamine into chitin, an important structural component in fungal cell walls. Powerful antifungal action in vivo has been most extensively studied with deep infections in models of dimorphic fungal infection. 4 NIKZ appears to