Impact of echinocandin on prognosis of proven invasive candidiasis in ICU: A post-hoc causal inference model using the AmarCAND2 study - 18/04/17

Doi : 10.1016/j.jinf.2016.12.016

Sébastien Bailly ^a,^⁎, Olivier Leroy ^b, Elie Azoulay ^c, Philippe Montravers ^d, Jean-Michel Constantin ^e, Hervé Dupont ^f, Didier Guillemot ^g, Olivier Lortholary ^h,ⁱ, Jean-Paul Mira ^j, Pierre-François Perrigault ^k, Jean-Pierre Gangneux ^l, Jean-François Timsit ^a,^m
AmarCAND2 Study Group
Hssain Aait, Adda, Allaouchiche, Ammenouche, Angel, Argaud, Badetti, Baldesi, Barthet, Bastien, Baudin, Bellec, Blasco, Bollaert, Bonadona, Bretonnière, Brocas, Brua, Bruder, Brunin, Cabaret, Carpentier, Cartier, Cerf, Chabanne, Charles, Cheval, Cinotti, Cohen, Constantin, Cousson, Delpierre, Demory, Diconne, Du Cheyron, Dubost, Dumenil, Durand, Duroy, Forel, Foucher-Lezla, Fratea, Gally, Gaudard, Geffe, Gergaud, Gette, Girault, Goubaux, Gouin, Grenot, Grossmith, Guelon, Guerin-Robardey, Guervilly, Hayl-Slayman, Hilbert, Houissa, Hraiech, Ichai, Jung, Kaidomar, Karoubi, Kherchache, Lambiotte, Lamhaut, Launoy, Lebreton, Lefrant, Lemaire, Lepape, Lepoivre, Leroy, Lesieur, Levy, Luyt, Mahe, Mahul, Mateu, Megarbane, Merle, Mira, Montcriol, Mootien, Navellou, Ouattara, Page, Perrigault, Petitpas, Plantefeve, Quinart, Quintard, Ragonnet, Roquilly, Ruiz, Saliba, Samba, Schmitt, Seguin, Sejourne, Tellier, Thevenot, Tonnelier, Van Grunderbeek, Vincent, Wiramus, Zogheib

^a Inserm UMR 1137 – IAME Team 5 – DeSCID: Decision Sciences in Infectious Diseases, Control and Care INSERM/ Paris Diderot, Sorbonne Paris Cité University, Paris, France
^b Medical ICU, Chatiliez Hospital, Tourcoing, France
^c Medical ICU, Saint-Louis University Hospital, Paris, France
^d Paris Diderot Sorbonne Cite University, and Anesthesiology and Critical Care Medicine, Bichat-Claude Bernard University Hospital, APHP, Paris, France
^e Perioperative Medicine Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France
^f Surgical ICU, Amiens University Hospital, Amiens, France
^g Inserm UMR 1181, Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases, (B2PHI), F-75015, Paris, France
^h University Paris Descartes, Necker Pasteur Center for Infectious Diseases, Necker Enfants-Malades Hospital, IHU Imagine, Paris, France
ⁱ Pasteur Institute, National Reference Center for Invasive Mycoses and Antifungals, CNRS URA3012, Paris, France
^j Medical ICU, Cochin University Hospital, APHP, and Paris Descartes, Sorbonne Paris Cité University, Paris, France
^k Medical-surgical ICU, Montpellier University Hospital, Montpellier, France
^l Mycology, Rennes University Hospital, Rennes, France
^m Medical ICU, Paris Diderot University/Bichat University Hospital, APHP, Paris, France

^∗Corresponding author.

Summary

Objective

guidelines recommend first-line systemic antifungal therapy (SAT) with echinocandins in invasive candidiasis (IC), especially in critically ill patients. This study aimed at assessing the impact of echinocandins compared to azoles as initial SAT on the 28-day prognosis in adult ICU patients.

Methods

From the prospective multicenter AmarCAND2 cohort (835 patients), we selected those with documented IC and treated with echinocandins (ECH) or azoles (AZO). The average causal effect of echinocandins on 28-day mortality was assessed using an inverse probability of treatment weight (IPTW) estimator.

Results

397 patients were selected, treated with echinocandins (242 patients, 61%) or azoles (155 patients, 39%); septic shock: 179 patients (45%). The median SAPSII was higher in the ECH group (48 [35; 62] vs. 43 [31; 58], p = 0.01). Crude mortality was 34% (ECH group) vs. 25% (AZO group). After adjustment on baseline confounders, no significant association emerged between initial SAT with echinocandins and 28-day mortality (HR: 0.95; 95% CI: [0.60; 1.49]; p = 0.82). However, echinocandin tended to benefit patients with septic shock (HR: 0.46 [0.19; 1.07]; p = 0.07).

Conclusion

Patients who received echinocandins were more severely ill. Echinocandin use was associated with a non-significant 7% decrease of 28-day mortality and a trend to a beneficial effect for patient with septic shock.

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Highlights

•	397 ICU patients with proven invasive candidiasis.
•	Treatment with azoles or echinocandins.
•	Echinocandins were more frequently administered to severely ill patients.
•	After adjustment, echinocandin use not associated with an improved 28-day prognosis.
•	A marginal beneficial effect of echinocandins for patients with concomitant septic shock.

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Keywords : Echinocandin, Fluconazole, Invasive candidiasis, Patient prognosis, IPTW estimator

Plan

Patient characteristics

SAT initiation and invasive candidiasis

Primary outcome

Secondary outcome

Discussion

Conflicts of interest

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Vol 74 - N° 4

P. 408-417 - avril 2017 Retour au numéro

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Impact of echinocandin on prognosis of proven invasive candidiasis in ICU: A post-hoc causal inference model using the AmarCAND2 study - 18/04/17

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