Inadequacy of fluconazole dosing in patients with candidemia based on Infectious Diseases Society of America (IDSA) guidelines

Abstract

Introduction: Based on Infectious Diseases Society of America (IDSA) guidelines, inappropriate fluconazole therapy in patients with candidemia is defined as an empiric dose <6 mg/kg/d, <12 mg/kg/d after Candida glabrata identification, or continued fluconazole use after identification of Candida krusei. However, the extent to which inappropriate antifungal therapy is due to improper dosing or drug selection has not been well investigated. The objectives of this study were to assess the incidence of inappropriate fluconazole therapy in patients with candidemia and to identify variables associated with inappropriate therapy.

Methods: Retrospective cohort study from four medical centers of hospitalized patients with candidemia prescribed fluconazole. Appropriateness of fluconazole dosages (adjusted for renal dysfunction) was assessed at the time of symptom onset and after Candida identification.

Results: Patients (206) were identified. Sixty-one of 112 (55%) patients who were given empiric therapy received an initial dose of fluconazole <6 mg/kg. After identification of the Candida species, 97 of 206 (47%) patients received inadequate fluconazole therapy based on IDSA guideline recommendations due to a fluconazole dose <12 mg/kg after isolation of C. glabrata (12%), continued use of fluconazole after isolation of C. krusei (3%), or a dose <6 mg/kg for all other Candida species (32%). Using multivariate logistic regression, increased weight in 1-kg increments (OR: 1.02; p = 0.0142) and a creatinine clearance (CRCL) >50 ml/minute (OR: 3.17; p = 0.0003) were associated with increased risk of inadequate fluconazole therapy.

Conclusion: A high prevalence of suboptimal dosing of fluconazole given empirically or after Candida species identification was documented. Increased weight and CRCL were significant predictors of inadequate fluconazole doses.