Evaluation of first-line therapies for the treatment of candidemia in ICU patients: A propensity score analysis

A. L. Bienvenu (1, 2) , P. Pradat (3) , C. Guerin (4) , F. Aubrun (5) , J. L. Fellahi (6, 7) , A. Friggeri (8, 9) , C. Guichon , R. Hernu , J. Menotti (10) , C. Monard (11) , S. Paulus , T. Rimmele (11) , V. Piriou (12) , C. Chidiac (13) , L. Argaud (14, 7) , G. Leboucher (15)

1 ICBMS - Institut de Chimie et Biochimie Moléculaires et Supramoléculaires
2 HCL - Hospices Civils de Lyon
3 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
4 ST-CROLLES - STMicroelectronics [Crolles]
5 Hôpital de la Croix-Rousse [CHU - HCL]
6 Service d'Anesthésie-Réanimation, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France
7 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
8 Service d'anesthésie-réanimation [Centre Hospitalier Lyon Sud - HCL]
9 LPE-Fondation Mérieux - Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory
10 Service de parasitologie et mycologie médicale [Hôpital de la Croix Rousse, Lyon]
11 Service d'Anesthésie-Réanimation, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France
12 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
13 Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL]
14 Hôpital Edouard Herriot, Service Anesthésie Réanimation
15 Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France

BACKGROUND: Candidemia is a major cause of mortality in the intensive care unit (ICU). According to the Infectious Diseases Society of America (IDSA), an echinocandin is recommended as initial therapy and fluconazole as an alternative. In a context of echinocandin resistance development, the question arising is whether azoles are a suitable alternative to echinocandins for the treatment of candidemia in critically ill patients. METHODS: A 3-year (2015-2017) retrospective multicentric cohort study was conducted. Adult patients with a diagnosis of candidemia during the ICU stay and treated with echinocandins or azoles were included. Demographic, clinical data, mycological data, and antifungal treatments were collected. Kaplan-Meier survival analysis, univariate analysis, and a multivariate logistic regression analysis using a propensity score with the inverse probability of treatment weighting method were performed. FINDINGS: Seventy-nine patients (n = 79) were analyzed. Treatment success, as well as survival on day 90 (Kaplan-Meier survival analysis, log rank test, p = 0.542), were comparable between patients who received echinocandins (caspofungin (n = 47)) or azoles (fluconazole (n = 29) or voriconazole (n = 3)). A multivariable analysis demonstrated that higher SOFA score on the day of candidemia diagnosis and absence of adequate Candida source control were independently associated with a greater risk of 90-day mortality, whereas azoles treatment was not associated with an excess 90-day mortality. INTERPRETATION: This study confirms that the use of azoles recommended for candidemia, mostly fluconazole, as a first-line therapy is a reasonable alternative to caspofungin for ICU patients in our institution. This needs to be included in local guidelines through antifungal stewardship programs.

Keywords: Female; Humans; Male; Middle Aged; Aged; Mortality; Treatment Outcome; Cohort Studies; Retrospective Studies; Critical Illness; Kaplan-Meier Estimate; *Intensive Care Units; Propensity Score; Antifungal Agents/*therapeutic use; Candidemia; Candidemia/*drug therapy/microbiology/mortality; Caspofungin; Caspofungin/*therapeutic use; Fluconazole; Fluconazole/*therapeutic use; Voriconazole; Voriconazole/therapeutic use

Domains: Life Sciences [q-bio]

A. L. Bienvenu, P. Pradat, C. Guerin, F. Aubrun, J. L. Fellahi, et al.. Evaluation of first-line therapies for the treatment of candidemia in ICU patients: A propensity score analysis. International Journal of Infectious Diseases, 2020, 93, pp.15--21. ⟨10.1016/j.ijid.2020.01.037⟩. ⟨hal-02901885⟩