title: MSG-01: A randomized, double-blind, placebo-controlled trial of caspofungin prophylaxis followed by preemptive therapy for invasive candidiasis in high-risk adults in the critical care setting.
abstract: BACKGROUND
  Invasive 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Caspofungin 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.
  
  
  BACKGROUND
  NCT00520234.
authors.affiliation: University of Texas Medical School at Houston and Memorial Hermann Texas Medical Center, Houston.
authors.forename: Luis
authors.initials: L
authors.lastname: Ostrosky-Zeichner
authors.forename: Shmuel
authors.initials: S
authors.lastname: Shoham
authors.forename: Jose
authors.initials: J
authors.lastname: Vazquez
authors.forename: Annette
authors.initials: A
authors.lastname: Reboli
authors.forename: Robert
authors.initials: R
authors.lastname: Betts
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Barron
authors.forename: Mindy
authors.initials: M
authors.lastname: Schuster
authors.forename: Marc A
authors.initials: MA
authors.lastname: Judson
authors.forename: Sanjay G
authors.initials: SG
authors.lastname: Revankar
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Caeiro
authors.forename: Julie E
authors.initials: JE
authors.lastname: Mangino
authors.forename: David
authors.initials: D
authors.lastname: Mushatt
authors.forename: Roger
authors.initials: R
authors.lastname: Bedimo
authors.forename: Alison
authors.initials: A
authors.lastname: Freifeld
authors.forename: Minh Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kauffman
authors.forename: William E
authors.initials: WE
authors.lastname: Dismukes
authors.forename: Andrew O
authors.initials: AO
authors.lastname: Westfall
authors.forename: Jeanna Beth
authors.initials: JB
authors.lastname: Deerman
authors.forename: Craig
authors.initials: C
authors.lastname: Wood
authors.forename: Jack D
authors.initials: JD
authors.lastname: Sobel
authors.forename: Peter G
authors.initials: PG
authors.lastname: Pappas
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D058365:Candidiasis, Invasive / Q000453:epidemiology / Q000517:prevention & control*; D000077336:Caspofungin; D004311:Double-Blind Method; D054714:Echinocandins / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D007362:Intensive Care Units; D055666:Lipopeptides; D008297:Male; D008875:Middle Aged; D065129:Pre-Exposure Prophylaxis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin
keywords: ICU; caspofungin; invasive candidiasis; preemptive therapy; prophylaxis