Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score–derived analysis of a population-based, multicentre prospective cohort

Abstract

We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia.

Is biofilm production a prognostic marker in adults with candidaemia?

“…In agreement with our findings, Lopez-Cortes et al studied a real-world prospective cohort of patients with candidaemia treated with empirical or targeted fluconazole and also did not observe an increase in 30-day mortality compared with patients treated with echinocandins. Furthermore, the use of fluconazole was not related to a higher incidence of clinical failure or persistent candidaemia, which, in fact, could more likely be associated with biofilm maintenance [28,29].…”

Intensive care medicine research agenda on invasive fungal infection in critically ill patients

“…Despite some studies showing the superiority of echinocandins over fluconazole, a propensity score-derived analysis of a population-based, multicenter prospective cohort has demonstrated that, in patients with candidemia, therapy with fluconazole did not show a significant association with mortality either in the empirical or targeted therapy [52]. These results were similar among patients with severe sepsis and septic shock.…”

Diagnosis and Treatment of Candidemia in the Intensive Care Unit

“…173 Targeted therapy is based on microbiological evidence of an IC (e.g., a positive blood culture for Candida species or positive cultures of a normally sterile site). 174 Moreover, once candidemia is diagnosed, an adequate source control of the infection (catheter removal, drainage, debridement) should be also performed as soon as possible. 3,27 Antifungal Agents…”

“…185 However, in a prospective study conducted in 29 hospitals in Spain with less severe patients (only 30% being in the ICU), empirical treatment with fluconazole was not associated with increased 30-day mortality compared with echinocandins in patients with candidemia. 174 There has been concern about the use of echinocandins as primary therapy against C. parapsilosis because of higher in vitro minimum inhibitory concentrations (MICs). A retrospective study on 307 episodes of C. parapsilosis candidemia demonstrated no difference in 30-day mortality between patients receiving an echinocandin as compared with fluconazole.…”