Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-8-13
pubmed:abstractText
We have previously reported poor correlation between the in vitro fungicidal activity of LY303366 and MIC results in RPMI medium based upon the manufacturer's suggested susceptibility endpoint, lack of visual growth. Additionally, we have noted a significant trailing effect with LY303366 when MICs are determined in RPMI medium. These observations have led us to evaluate an alternative susceptibility endpoint for LY303366, an 80% reduction in growth compared with control (similar to that utilized for azoles). Two isolates each of Candida albicans, Candida glabrata, and Candida tropicalis were selected for testing. MICs were determined for LY303366 in RPMI 1640 medium buffered with morpholinepropanesulfonic acid. MICs were determined with suggested (MIC100) and experimental (MIC80) endpoints. The minimal fungicidal concentration (MFC) of LY303366 for each isolate was also determined. Time-kill curves were determined in RPMI medium with each isolate at concentrations of LY303366 ranging from 0.125 to 16x MIC80 to assess the correlation between MIC80 and fungicidal activity. Lastly, fungi exposed to LY303366 were examined via scanning electron microscope (SEM) for evidence of drug-induced ultrastructure change. MIC80s for test isolates ranged from 0.015 to 0.12 microgram/ml and were consistently three to five wells less than MIC100s. Good correlation was observed between fungicidal activity, as assessed by kill curves, and the MIC80. SEM data revealed significant ultrastructure changes induced by LY303366 even at sub-MIC80s. Based on our results demonstrating better correlation between MIC80 and fungicidal activity, i.e., time-kill curves and MFCs, we suggest that 80% reduction in visible growth be utilized as the endpoint for susceptibility determinations with LY303366 in RPMI medium.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0066-4804
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1387-91
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Evaluation of endpoints for antifungal susceptibility determinations with LY303366.
pubmed:affiliation
College of Pharmacy, University of Iowa, Iowa City 52242, USA. michaelklepser@uiowa.edu
pubmed:publicationType
Journal Article