Survival in Patients with Candida glabrata Bloodstream Infection Is Associated with Fluconazole Dose

Abstract

Robust pharmacodynamic indices that align fluconazole dose or exposure with outcomes in invasive candidiasis due to Candida glabrata remain elusive. The purpose of this retrospective multicenter study was to evaluate a cohort of 127 patients with C. glabrata fungemia treated with fluconazole, using adjusted analyses to identify risk factors for 28-day death. No significant correlations were found between fluconazole area under the curve (AUC), AUC/MIC ratio, or MIC and survival. In multivariate logistic regression analyses, however, higher average fluconazole dose (odds ratio [OR], 1.006 [95% confidence interval [CI], 1.001 to 1.010]; P = 0.008), average fluconazole dose of ≥400 mg (OR, 3.965 [95% CI, 1.509 to 10.418]; P = 0.005), and higher fluconazole dose on day 1 of therapy (OR, 1.007 [95% CI, 1.002 to 1.011]; P = 0.002) were found to be independent predictors of 28-day survival. Additionally, the presence of a central venous catheter at the time of infection was found to be a significant risk factor for death. In conclusion, we found fluconazole dose to be an independent predictor of 28-day survival for patients with C. glabrata fungemia, with doses of ≥400 mg/day being associated with 28-day survival rates approaching 90%. These data indicate the use and efficacy of fluconazole in the treatment of this serious infection. Aggressive dosing appears to be necessary when fluconazole is used for the treatment of C. glabrata fungemia, irrespective of MIC.

Keywords: Candida glabrata; bloodstream infection; fluconazole; pharmacodynamics.

FIG 1

Survival at day 28, stratified by fluconazole dose.