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Antimicrobial Agents and Chemotherapy, October 2001, p. 2781-2786, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2781-2786.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Differential Antifungal Activity of Isomeric Forms of Nystatin

Luis Ostrosky-Zeichner,1,* Scott Bazemore,2 Victor L. Paetznick,1 Jose R. Rodriguez,1 Enuo Chen,1 Tom Wallace,2 Paul Cossum,2 and John H. Rex1

Laboratory of Mycology Research, Division of Infectious Diseases, Department of Internal Medicine, and Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Houston Medical School, Houston, Texas 77030,1 and Aronex Pharmaceuticals, The Woodlands, Texas 773812

Received 1 February 2001/Returned for modification 31 May 2001/Accepted 19 July 2001

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 >= 8× 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.

* Corresponding author. Mailing address: Division of Infectious Diseases, 6431 Fannin, JFB 1.728, Houston, TX 77030. Phone: (713) 500-5388. Fax: (713) 500-5495. E-mail: Luis.Ostrosky-Zeichner{at}uth.tmc.edu.

Antimicrobial Agents and Chemotherapy, October 2001, p. 2781-2786, Vol. 45, No. 10
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.10.2781-2786.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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