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David Calabrese

Publications and source records attributed to David Calabrese.

3 recordsLinked to original sources
PubMed2000

A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole.

Azole resistance in Candida albicans can be mediated by several resistance mechanisms. Among these, alterations of the azole target enzyme and the overexpression of multidrug efflux transporter genes are the most frequent. To identify additional putative azole resistance genes in C. albicans, a genomic library from this organism was screened for complementation of fluconazole hypersusceptibility in Saccharomyces cerevisiae YKKB-13 lacking the ABC (ATP-binding cassette) transporter gene PDR5. Among the C. albicans genes obtained, a new gene was isolated and named FLU1 (fluconazole resistance). The deduced amino acid sequence of FLU1 showed similarity to CaMDR1 (formerly BEN(r)), a member of the major facilitator superfamily of multidrug efflux transporters. The expression of FLU1 in YKKB-13 mediated not only resistance to fluconazole but also to cycloheximide among the different drugs tested. The disruption of FLU1 in C. albicans had only a slight effect on fluconazole susceptibility; however, it resulted in hypersusceptibility to mycophenolic acid, thus suggesting that this compound could be a substrate for the protein encoded by FLU1. Disruption of FLU1 in a background of C. albicans mutants with deletions in several multidrug efflux transporter genes, including CDR1, CDR2 and CaMDR1, resulted in enhanced susceptibility to several azole derivatives. FLU1 expression did not vary significantly between several pairs of azole-susceptible and azole-resistant C. albicans clinical isolates. Therefore, FLU1 seems not to be required for the development of azole resistance in clinical isolates.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

Restocking the sample closet: results of a trial to alter medication prescribing.

BACKGROUND: Although medication costs make up a large and growing portion of health care costs, few interventions have successfully encouraged physicians to alter prescribing patterns. METHODS: To promote the use of an open formulary, we altered the contents of the sample closets of five primary care practices in eastern Massachusetts. In these practices, we removed all nonformulary drugs in five drug classes and restocked with purchased generic samples. We performed a time series analysis of formulary compliance, before and during an 8-month intervention, with five concurrent control practices for comparison. RESULTS: Although providers in both the intervention and control practices complied well with the formulary, we found no incremental effect of the sample closet intervention on absolute formulary compliance (P = .46) or on the secular trend in formulary compliance (P = .60). We also found no effect on these measures in any of the individual drug classes studied. CONCLUSIONS: This sample closet intervention did not appear to improve further the good formulary compliance in these practices. In such settings, better ways are needed to guide prescribing behavior.

Boston↗