• Sébastien Bailly, Lila Bouadma, Elie Azoulay, Orgeas Maité Garrouste MG, Christophe Adrie, Bertrand Souweine, Carole Schwebel, Danièle Maubon, Rebecca Hamidfar-Roy, Michael Darmon, Michel Wolff, Muriel Cornet, and Jean-François Timsit.
• 1 Grenoble 1 University, U823, La Tronche, France.
• Am. J. Respir. Crit. Care Med. 2015 May 15; 191 (10): 1139-46.

RationaleSystemic antifungal treatments are empirically administered to the sickest critically ill patients, often without documented invasive fungal infection.ObjectivesTo estimate the impact of systemic antifungal treatment on 30-day survival of patients suspected to have invasive candidiasis.MethodsAll nonneutropenic, nontransplant recipients managed in five intensive care units intubated for at least 5 days, and free of invasive candidiasis, were included. To account for differences in patients' characteristics recorded daily before study end point, a causal model for longitudinal data was used to assess benefits from antifungal treatment. The composite primary end point was hospital mortality or occurrence of invasive candidiasis.Measurements And Main ResultsAmong 1,491 patients, 100 (6.7%) received antifungal treatment for a suspected infection. Patients treated with antifungals were more severely ill than untreated patients. Within the 30-day follow-up period, 363 (24.3%) patients died, and 22 (1.5%) exhibited documented invasive candidiasis. After adjustment on baseline and time-dependent confounders (underlying illness, severity, invasive procedures, Candida colonization), and using a marginal structural model for longitudinal data, treatment was not associated with a decreased risk of mortality or of occurrence of invasive candidiasis (hazard ratio, 1.05; 95% confidence interval, 0.56-1.96; P = 0.91).ConclusionsThis study failed to show outcome benefits for empirical systemic antifungal therapy in the sickest critically ill, nonneutropenic, nontransplanted patients. The post hoc power did not allow us to conclude to an absence of treatment effect especially for specific subgroups. Studies to refine indications for empirical treatment based on surrogate markers of invasive candidiasis are warranted.

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