title: Differential antifungal activity of isomeric forms of nystatin.
abstract: When nystatin is placed in RPMI and other biological fluids, there is loss of pure nystatin, with the development of two distinguishable chromatographic peaks, 1 and 2. Peak 1 appears identical to commercially prepared nystatin. By nuclear magnetic resonance (NMR) and mass spectral analysis, peak 2 appears to be an isomer of peak 1. The isomers are quantitatively and fully interconvertible. Formation of peak 2 is accelerated at a pH of >7.0 and ultimately reaches a near 55:45 (peak 1/peak 2 ratio) mixture. We sought to determine the relative activities of peaks 1 and 2 against Candida spp. Peak 2 consistently showed higher MICs when it was the predominant form during the experiment. Time-kill analyses showed that peak 2 required > or =8 x the concentration of peak 1 to produce a modest and delayed killing effect, which was never of the same magnitude as that produced by peak 1. In both types of assays, the activity of peak 2 corresponded with intra-assay formation of peak 1. Both MIC measurements and time-kill analysis suggest that peak 2 has considerably less activity, if any at all, against Candida spp. Peak 2 may serve as a reservoir for peak 1.
authors.affiliation: Laboratory of Mycology Research, Division of Infectious Diseases, Department of Internal Medicine, University of Texas Houston Medical School, 6431 Fannin, Houston, TX 77030, USA. Luis.Ostrosky-Zeichner@uth.tmc.edu
authors.forename: L
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.forename: S
authors.initials: S
authors.lastname: Bazemore
authors.forename: V L
authors.initials: VL
authors.lastname: Paetznick
authors.forename: J R
authors.initials: JR
authors.lastname: Rodriguez
authors.forename: E
authors.initials: E
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Wallace
authors.forename: P
authors.initials: P
authors.lastname: Cossum
authors.forename: J H
authors.initials: JH
authors.lastname: Rex
mesh_terms: D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D002845:Chromatography; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D009761:Nystatin / Q000302:isolation & purification / Q000494:pharmacology*; D020033:Protein Isoforms / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D020033:Protein Isoforms; D009761:Nystatin