• Luis Ostrosky-Zeichner, Shmuel Shoham, Jose Vazquez, Annette Reboli, Robert Betts, Michelle A Barron, Mindy Schuster, Marc A Judson, Sanjay G Revankar, Juan Pablo Caeiro, Julie E Mangino, David Mushatt, Roger Bedimo, Alison Freifeld, Minh Hong Nguyen, Carol A Kauffman, William E Dismukes, Andrew O Westfall, Jeanna Beth Deerman, Craig Wood, Jack D Sobel, and Peter G Pappas.
• University of Texas Medical School at Houston and Memorial Hermann Texas Medical Center, Houston.
• Clin. Infect. Dis. 2014 May 1; 58 (9): 1219-26.

BackgroundInvasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.ResultsThe incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P = .14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P = .04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.ConclusionsCaspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials RegistrationNCT00520234.

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