title: Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards.
abstract: The availability of reproducible antifungal susceptibility testing methods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In this paper, we have examined the conceptual framework underlying interpretation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respective manufacturers that correlate fluconazole and itraconazole MICs with outcome of candidal infections. Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinical Laboratory Standards' M27-T broth macrodilution methodology are proposed: isolates for which MICs are < or = 8 microg/mL are susceptible to fluconazole, whereas those for which MICs are > or = 64 microg/mL appear resistant. Isolates for which the MIC of fluconazole is 16-32 microg/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response when > 100 mg of fluconazole per day is given. These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resistant to fluconazole. Tentative interpretive MIC breakpoints for itraconazole apply only to mucosal candidal infections and are as follows: susceptible, < or = 0.125 microg/mL; S-DD, 0.25-0.5 microg/mL; and resistant, > or = 1.0 microg/mL. These tentative breakpoints are now open for public commentary.
authors.affiliation: Department of Internal Medicine, Center for the Study of Emerging and Reemerging Pathogens, University of Texas Medical School, Houston, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Rex
authors.forename: M A
authors.initials: MA
authors.lastname: Pfaller
authors.forename: J N
authors.initials: JN
authors.lastname: Galgiani
authors.forename: M S
authors.initials: MS
authors.lastname: Bartlett
authors.forename: A
authors.initials: A
authors.lastname: Espinel-Ingroff
authors.forename: M A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: M
authors.initials: M
authors.lastname: Lancaster
authors.forename: F C
authors.initials: FC
authors.lastname: Odds
authors.forename: M G
authors.initials: MG
authors.lastname: Rinaldi
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: A L
authors.initials: AL
authors.lastname: Barry
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002177:Candidiasis / Q000188:drug therapy*; D004352:Drug Resistance, Microbial; D015725:Fluconazole / Q000494:pharmacology*; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D015725:Fluconazole