title: A Risk Score for Fluconazole Failure among Patients with Candidemia.
abstract: This study aimed to develop a prediction model to identify patients with candidemia who were at high risk of failing fluconazole treatment. Adult patients in the United States with candidemia who received fluconazole during hospitalization were selected from the Cerner Health Facts Hospital Database (04/2004 to 03/2013). Fluconazole failure was defined as switching/adding another antifungal, positiveCandidaculture ≥10 days after fluconazole initiation, or death during hospitalization. Patients were randomized into modeling and validation samples. Using the modeling sample, a regression analysis of least absolute shrinkage and selection operator was used to select risk predictors of fluconazole failure (demographics,Candidaspecies, initiation of fluconazole before positive culture and after admission, and comorbidities, procedures, and treatments during the 6 months before admission and fluconazole initiation). The prediction model was evaluated using the validation sample. We found that of 987 identified patients (average age of 61 years, 51% male, 72% Caucasian), 49% failed and 51% did not fail fluconazole treatment. Of those who failed, 70% switched or added another antifungal, 21% had a second positiveCandidatest, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission,Candida glabrataorCandida kruseiinfection, hematological malignancy, venous thromboembolism (VTE), enteral nutrition, use of nonoperative intubation/irrigation, and other antifungal use. All but VTE were associated with a higher risk of failure. The model's c-statistic was 0.65, with a Hosmer-Lemeshow testPvalue of 0.23. In summary, this prediction model identified patients with a high risk of fluconazole failure, illustrating the potential value and feasibility of personalizing candidemia treatment.
authors.affiliation: Division of Infectious Diseases, McGovern Medical School, Houston, Texas, USA Luis.Ostrosky-Zeichner@uth.tmc.edu.
authors.forename: Luis
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.affiliation: Astellas Pharma US, Northbrook, Illinois, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Harrington
authors.affiliation: Astellas Pharma US, Northbrook, Illinois, USA.
authors.forename: Nkechi
authors.initials: N
authors.lastname: Azie
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts, USA.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Yang
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts, USA.
authors.forename: Nanxin
authors.initials: N
authors.lastname: Li
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts, USA.
authors.forename: Valerie
authors.initials: V
authors.lastname: Koo
authors.affiliation: Analysis Group, Inc., Boston, Massachusetts, USA.
authors.forename: Eric Q
authors.initials: EQ
authors.lastname: Wu
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects*; D058387:Candidemia / Q000188:drug therapy* / Q000401:mortality*; D025141:Drug Resistance, Fungal; D005260:Female; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008962:Models, Theoretical; D012307:Risk Factors; D017211:Treatment Failure
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole
keywords: Candida; candidemia; failure; fluconazole; invasive candidiasis; risk score