OSTROSKY-ZEICHNER L, BAZEMORE SA, PAETZNICK VL, RODRIGUEZ JR, CHEN E, WALLACE TL, REX JH; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 395.
Univ. of Texas Houston Med. Sch., Houston, TX
BACKGROUND: When NYS is placed in RPMI or used in vivo, there is a quantitative change of native NYS (P1) to a 2nd chromatographic peak (P) termed P2. By mass spec and NMR, P2 is an isomer of P1. P2 formation accelerates at pH > 7.0, ultimately reaching a 50-50 mixture with P1. P1 & P2 are interconvertible, but P1 can be maintained in relatively pure form at pH 6.0. We sought to determine if P1 & P2 are both active against Candida spp.METHODS: We measured MICs at 24h by NCCLS M-27 (MIC = least concentration giving a clear well) in RPMI + 0.075 M MOPS + 0.075 M MES (2-(N-Morpholino)ethanesulfonic acid, gives a buffering range of pH 5.5-7.9). P1 & P2 were separated by HPLC. Time-kill testing followed Klepser (AAC 1998; 42:1207-12).RESULTS: Amphotericin B (AmB), NYS, and P1 MICs changed by = 1 dilution between pH 6 and 7.5 (table). P2 consistently showed less activity when it was the predominant form during the experiment. The data are limited by P1-P2 inter-conversion during the 24h assay period [table: see text]. In time-kill studies with 34028074, P2 required >/= 8x the concentration of P1 to produce a modest & delayed killing effect that was never of the same magnitude as that of P1. The activity of P2 corresponded best with intra-assay P1 formation. Discussion: Although limited by P1-2 inter-conversion, MIC measurements and time-kill analysis suggest that P1 is the principal active component of NYS. P2 can convert to P1 and could act as a reservoir for P1.KEYWORDS: Antifungal activity; Candida spp.; Nystatin
Publication Types:
Keywords:
- Amphotericin B
- Antifungal Agents
- Buffers
- Candida
- Miconazole
- Microbial Sensitivity Tests
- Nystatin
Other ID:
UI: 102248058
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