Survival in Patients with Candida glabrata Bloodstream Infections is Associated with Fluconazole Dose [PublishAheadOfPrint]

Robust pharmacodynamic indices that align fluconazole dose or exposure with outcome in invasive candidiasis due to C. 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 mortality. No significant correlations were found between fluconazole AUC, AUC:MIC, or MIC and survival. However, on multivariable logistic regression, higher average fluconazole dose (odds ratio (OR) 1.006, 95% confidence interval (CI), 1.001-1.010, p=0.008), average fluconazole dose ≥ 400 mg (OR 3.965, 95% CI 1.509-10.418, p=0.005), and higher fluconazole dose on day 1 of therapy (OR 1.007, 95% CI 1.002-1.011, 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 mortality. In conclusion, we found fluconazole dose to be an independent predictor for 28-day survival in patients with C. glabrata fungemia, with doses ≥ 400mg/day associated with 28-day survival approaching 90%. These data inform the use and efficacy of fluconazole in the treatment of this serious infection. Aggressive dosing appears necessary when using fluconazole for the treatment of C. glabrata fungemia, irrespective of MIC.

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