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. 2021 Apr 20:8:641965.
doi: 10.3389/fmed.2021.641965. eCollection 2021.

No Impact of Fluconazole to Echinocandins Replacement as First-Line Therapy on the Epidemiology of Yeast Fungemia (Hospital-Driven Active Surveillance, 2004-2017, Paris, France)

Stéphane Bretagne  1   2   3 , Marie Desnos-Ollivier  1 , Karine Sitbon  1 , Olivier Lortholary  1   3   4 , Didier Che  5 , Françoise Dromer  1 ; Participants of the YEASTS
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No Impact of Fluconazole to Echinocandins Replacement as First-Line Therapy on the Epidemiology of Yeast Fungemia (Hospital-Driven Active Surveillance, 2004-2017, Paris, France)

Stéphane Bretagne et al. Front Med (Lausanne). .

Abstract

Replacement of fluconazole by echinocandins as the first-line therapy for yeast-related fungemia could have an impact on both the mortality rate and the epidemiology of yeast species responsible for candidemia. We analyzed the individual clinical and microbiological data collected through the active surveillance program on yeast fungemia (YEASTS program, 2004-2016, Paris area, France) within 14 University Hospitals. The cohort included 3,092 patients [male:female ratio: 1.56; median age 61.0 years (IQR: 23.8)]. The mean mortality rate within 30 days was 38.5% (1,103/2,868) and significantly higher in intensive care units (690/1,358, 50.8%) than outside (413/1,510, 27.4%, p < 0.0001) without significant change over time. The yeast species distribution [Candida albicans (n = 1,614, 48.0%), Candida glabrata (n = 607, 18.1%), Candida parapsilosis (n = 390, 11.6%), Candida tropicalis (n = 299, 8.9%), Candida krusei (n = 96, 2.9%), rare species (n = 357, 10.6%)], minimal inhibitory concentration distribution, and the distribution between the patient populations (hematological malignancies, solid tumors, without malignancy) did not change either while the proportion of patients ≥60-years increased from 48.7% (91/187) in 2004 to 56.8% (133/234) in 2017 (p = 0.0002). Fluconazole as first-line therapy dramatically decreased (64.4% in 2004 to 27.7% in 2017, p < 0.0001) with a corresponding increase in echinocandins (11.6% in 2004 to 57.8% in 2017, p < 0.0001). Survival rates did not differ according to the first antifungal therapy. The progressive replacement of fluconazole by echinocandins as the first-line antifungal therapy was not associated with change in global mortality, regardless of species involved and antifungal susceptibility profiles. Other factors remain to be uncovered to improve the prognosis of yeast fungemia.

Keywords: candidemia; echinocandins; epidemiology; fluconazole; fungemia; hematological malignancy; intensive care unit; solid cancer.

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Conflict of interest statement

SB has received travel grant from Pfizer in 2018 and has served on scientific advisory board for Gilead until 2018. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Evolution of global mortality and first-line antifungal drug prescription in patients with hematological malignancy, oncology or no malignancy, inside or outside intensive care unit (ICU) (YEASTS program, Paris area, 2004–2017). (A) Global mortality did not change significantly over time inside (solid black line) and outside (dotted black line) ICU in the various categories of patients. (B) The evolution of fluconazole (solid blue line) and echinocandins (dotted blue line) prescription significantly (p < 0.001) differed inside and outside ICU in the three populations of patients. The switch from fluconazole to echinocandins as first-line therapy did not occur at the same date in the six populations studied.
Figure 2
Figure 2
Stable global distribution of species responsible for fungemia during the YEASTS program (Paris area, 2004–2017). Figures in the histograms indicate the number of fungemia due to the five more frequent species, the last category regrouping fungemia due to rare species (<2% of isolates) or to mixed species. A total of 3,363 isolates was recovered during 3,257 episodes in 3,092 patients. The black line represents the evolution of the number of episodes over time (linear regression, R2 = 0.5101).
Figure 3
Figure 3
Evolution of first-line antifungal drug prescription for treatment of yeast fungemia (YEAST program, Paris area, 2004–2017). First-line treatment was analyzed for the 2,677 episodes for which time to potential death exceeded 48 h. Figures represent the number of episodes treated each year by fluconazole alone, echinocandin alone, other treatments (liposomal amphotericin B, voriconazole, posaconazole, itraconazole, or drug combination), or not treated.
Figure 4
Figure 4
Kaplan–Meier curves illustrating survival rate after incident candidemia according to the species involved in case of single infection due to the five major species or to rare or mixed species (YEASTS program, Paris area, 2004–2017)—(logrank-test p < 0.0001). Survival following infection with C. albicans (solid blue line), C. glabrata (dashed blue line), C. parapsilosis (dashed gray line), C. tropicalis (solid gray line), rare or mixed species (solid black line) are presented. Compared to C. albicans, survival probability was lower with C. krusei (p = 0.0070) and better with C. parapsilosis (p < 0.0001).
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