Selection of a surrogate agent (fluconazole or voriconazole) for initial susceptibility testing of posaconazole against Candida spp.: results from a global antifungal surveillance program

M A Pfaller; S A Messer; L Boyken; S Tendolkar; R J Hollis; D J Diekema

doi:10.1128/JCM.01952-07

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Selection of a surrogate agent (fluconazole or voriconazole) for initial susceptibility testing of posaconazole against Candida spp.: results from a global antifungal surveillance program

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Selection of a surrogate agent (fluconazole or voriconazole) for initial susceptibility testing of posaconazole against Candida spp.: results from a global antifungal surveillance program

M A Pfaller, S A Messer, L Boyken, S Tendolkar, R J Hollis and D J Diekema

Journal of clinical microbiology, Vol.46(2), pp.551-559

02/2008

DOI: 10.1128/JCM.01952-07

PMCID: PMC2238086

PMID: 18094129

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Abstract

There are currently no FDA-approved broth microdilution antifungal susceptibility testing products or interpretive breakpoints for susceptibility testing of the new triazole posaconazole. Fluconazole and voriconazole are in the same triazole class as posaconazole, have CLSI-approved interpretive MIC breakpoints, and are available on some commercially available MIC panels. We investigated whether one or both of these agents may be useful as a surrogate marker for posaconazole susceptibility. Fluconazole, voriconazole, and posaconazole MIC results for 10,807 isolates of Candida spp. were analyzed to validate a potential surrogate marker for posaconazole activity against indicated species. For illustrative purposes, we applied the voriconazole MIC breakpoints to posaconazole (susceptible, < or =1 microg/ml; susceptible dose dependent, 2 microg/ml; resistant, > or =4 microg/ml) and compared these MIC results and categorical interpretations with those of fluconazole and voriconazole by using regression statistics and categorical agreement. For all 10,807 isolates, the absolute categorical agreement was 91.1% (0.1% very major errors [VME], 1.2% major errors [ME], and 7.6% minor errors [M]) using fluconazole as the surrogate marker and 97.7% (0.3% VME 0.1% ME, and 1.9% M) using voriconazole as the surrogate. The results with fluconazole improved to a categorical agreement of 93.7% (0.1% VME, 0.2% ME, and 6.0% M) when results for Candida krusei (not indicated for fluconazole testing) were omitted. Either fluconazole or voriconazole MIC results may serve as surrogate markers to predict the susceptibility of Candida spp. to posaconazole.

Antifungal Agents - pharmacology

Triazoles - pharmacology

Regression Analysis

Fluconazole - pharmacology

Humans

Voriconazole

Biomarkers

Candida - drug effects

Pyrimidines - pharmacology

Candidiasis - microbiology

Candida - isolation & purification

Microbial Sensitivity Tests - methods

Details

Title: Subtitle: Selection of a surrogate agent (fluconazole or voriconazole) for initial susceptibility testing of posaconazole against Candida spp.: results from a global antifungal surveillance program
Creators: M A Pfaller - Medical Microbiology Division, C606 GH, Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242, USA. michael-pfaller@uiowa.edu
S A Messer
L Boyken
S Tendolkar
R J Hollis
D J Diekema
Resource Type: Journal article
Publication Details: Journal of clinical microbiology, Vol.46(2), pp.551-559
DOI: 10.1128/JCM.01952-07
PMID: 18094129
PMCID: PMC2238086
NLM abbreviation: J Clin Microbiol
ISSN: 0095-1137
eISSN: 1098-660X
Publisher: United States
Language: English
Date published: 02/2008
Academic Unit: Infectious Diseases; Epidemiology; Pathology; Internal Medicine
Record Identifier: 9983986370402771

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