MSG-01: A randomized, double-blind, placebo controlled trial of caspofungin prophylaxis followed by pre-emptive therapy for invasive candidiasis in high-risk adults in the critical care setting.
Clin Infect Dis. 2014 Feb 18;
Authors: Ostrosky-Zeichner L, Shoham S, Vazquez J, Reboli A, Betts R, Barron MA, Schuster M, Judson MA, Revankar SG, Caeiro JP, Mangino JE, Mushatt D, Bedimo R, Freifeld A, Nguyen MH, Kauffman CA, Dismukes WE, Westfall AO, Deerman JB, Wood C, Sobel JD, Pappas PG
Background. Invasive candidiasis is the 3rd most common bloodstream infection in the ICU and is associated with morbidity and mortality. Prophylaxis and pre-emptive therapy are attractive strategies for this setting. Methods. We conducted a multicenter, randomized, double-blind, placebo controlled trial of caspofungin vs. placebo 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 one additional risk factor: parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other Immunosuppressants. (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 pre-emptive therapy with caspofungin. The pre-emptive approach analysis included patients all patients who received study drug, including those positive at baseline. Results. For prophylaxis, the incidence of proven or probable invasive candidiasis in the placebo vs. caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively (p= 0.14). For the pre-emptive approach analysis it was 30.4% (31/102) and 18.8% (22/117), respectively (p= 0.04), 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. Conclusion. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis but the difference was not statistically significant. A pre-emptive therapy approach deserves further study.
PMID: 24550378 [PubMed - as supplied by publisher]