title: Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patient-level quantitative review of randomized trials.
abstract: BACKGROUND
  Invasive candidiasis (IC) is an important healthcare-related infection, with increasing incidence and a crude mortality exceeding 50%. Numerous treatment options are available yet comparative studies have not identified optimal therapy.
  
  
  METHODS
  We conducted an individual patient-level quantitative review of randomized trials for treatment of IC and to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Studies were identified by searching computerized databases and queries of experts in the field for randomized trials comparing the effect of ≥2 antifungals for treatment of IC. Univariate and multivariable analyses were performed to determine factors associated with patient outcomes.
  
  
  RESULTS
  Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, and the rate of treatment success was 67.4%. Logistic regression analysis for the aggregate data set identified increasing age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02; P = .02), the Acute Physiology and Chronic Health Evaluation II score (OR, 1.11; 95% CI, 1.08-1.14; P = .0001), use of immunosuppressive therapy (OR, 1.69; 95% CI, 1.18-2.44; P = .001), and infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P = .01) as predictors of mortality. Conversely, removal of a central venous catheter (CVC) (OR, 0.50; 95% CI, .35-.72; P = .0001) and treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) were associated with decreased mortality. Similar findings were observed for the clinical success end point.
  
  
  CONCLUSIONS
  Two treatment-related factors were associated with improved survival and greater clinical success: use of an echinocandin and removal of the CVC.
authors.affiliation: University of Wisconsin, 1685 Highland Ave, Medical Foundation Centennial Building, Madison, WI 53705, USA. dra@medicine.wisc.edu
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.forename: Nasia
authors.initials: N
authors.lastname: Safdar
authors.forename: John W
authors.initials: JW
authors.lastname: Baddley
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Playford
authors.forename: Annette C
authors.initials: AC
authors.lastname: Reboli
authors.forename: John H
authors.initials: JH
authors.lastname: Rex
authors.forename: Jack D
authors.initials: JD
authors.lastname: Sobel
authors.forename: Peter G
authors.initials: PG
authors.lastname: Pappas
authors.forename: Bart Jan
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage*; D058365:Candidiasis, Invasive / Q000188:drug therapy*; D002405:Catheterization, Central Venous / Q000009:adverse effects; D054714:Echinocandins / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins