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, positive Candida culture Ն10 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, Candida species, 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 positive Candida test, and 42% died during hospitalization. Nine risk factors were included in the prediction model: days to start fluconazole after admission, Candida glabrata or Candida krusei infection, 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 test P value 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.

Inhibitory effect of menthol on expression of aspartyl proteinase 1 in fluconazole-resistant Candida albicans

“…The results presented in this paper showed 100% of resistancy in C. albicans vaginal isolates to fluconazole. These results are corroborated by the literature, citing fluconazole-resistant C. albicans (27)(28)(29). Fluconazole is a fungistatic rather than fungicidal medication and hence provides the opportunity for acquired resistance in certain fungi (29).…”

“…Fluconazole resistance has been identified as the main cause of treatment failure of candidiasis (27,28). Considering a major clinical challenge of antifungal resistance, the antimicrobial potential of the natural products can be regarded as a precious resource.…”

Comparative Assessment of Matrix-assisted Laser Desorption Ionization-time of Flight Mass Spectrometry (MALDI-TOF-MS) and Conventional Methods in the Identification of Clinically Relevant Yeasts

“…In a recent study on C. krusei, it was demonstrated that early fluconazole therapy did not affect the mortality rate. Thus, the correct Identification of C. krusei could find a survival benefit when early, appropriate antifungal therapy is administered [11].…”

Distribution of Yeast Species and Risk Factors of Oral Colonization among the Residents at Nursing Homes in Taiwan

“…The fact that different Candida species have different susceptibilities to antifungal drugs illustrates the potential for personalizing candidemia treatment [37]. For example, fluconazole, one of the most commonly prescribed antifungal drugs, is not suggested to treat infections caused by C. krusei or C. glabrata [38].…”