title: Evaluation by data mining techniques of fluconazole breakpoints established by the Clinical and Laboratory Standards Institute (CLSI) and comparison with those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST).
abstract: The EUCAST and the CLSI have established different breakpoints for fluconazole and Candida spp. However, the reference methodologies employed to obtain the MICs provide similar results. The aim of this work was to apply supervised classification algorithms to analyze the clinical data used by the CLSI to establish fluconazole breakpoints for Candida infections and to compare these data with the results obtained with the data set used to set up EUCAST fluconazole breakpoints, where the MIC for detecting failures was >4 mg/liter, with a sensitivity of 87%, a false-positive rate of 8%, and an area under the receiver operating characteristic (ROC) curve of 0.89. Five supervised classifiers (J48 and CART decision trees, the OneR decision rule, the naïve Bayes classifier, and simple logistic regression) were used to analyze the original cohort of patients (Rex's data set), which was used to establish CLSI breakpoints, and a later cohort of candidemia (Clancy's data set), with which CLSI breakpoints were validated. The target variable was the outcome of the infections, and the predictor variable was the MIC or dose/MIC ratio. For Rex's data set, the MIC detecting failures was >8 mg/liter, and for Clancy's data set, the MIC detecting failures was >4 mg/liter, in close agreement with the EUCAST breakpoint (MIC > 4 mg/liter). The sensitivities, false-positive rates, and areas under the ROC curve obtained by means of CART, the algorithm with the best statistical results, were 52%, 18%, and 0.7, respectively, for Rex's data set and 65%, 6%, and 0.72, respectively, for Clancy's data set. In addition, the correlation between outcome and dose/MIC ratio was analyzed for Clancy's data set, where a dose/MIC ratio of >75 was associated with successes, with a sensitivity of 93%, a false-positive rate of 29%, and an area under the ROC curve of 0.83. This dose/MIC ratio of >75 was identical to that found for the cohorts used by EUCAST to establish their breakpoints (a dose/MIC ratio of >75, with a sensitivity of 91%, a false-positive rate of 10%, and an area under the ROC curve of 0.90).
authors.affiliation: Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cuesta
authors.forename: Concha
authors.initials: C
authors.lastname: Bielza
authors.forename: Manuel
authors.initials: M
authors.lastname: Cuenca-Estrella
authors.forename: Pedro
authors.initials: P
authors.lastname: Larrañaga
authors.forename: Juan L
authors.initials: JL
authors.lastname: Rodríguez-Tudela
mesh_terms: D000047:Academies and Institutes; D026683:Advisory Committees; D000465:Algorithms; D000935:Antifungal Agents / Q000008:administration & dosage*; D001499:Bayes Theorem; D002175:Candida / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D057225:Data Mining / Q000379:methods; D003663:Decision Trees; D004305:Dose-Response Relationship, Drug; D005060:Europe; D015725:Fluconazole / Q000008:administration & dosage*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000592:standards* / Q000706:statistics & numerical data*; D012372:ROC Curve
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole