title: Timing of susceptibility-based antifungal drug administration in patients with Candida bloodstream infection: correlation with outcomes.
abstract: OBJECTIVE
  We sought to determine the impact of timing of appropriate antifungal therapy, as assessed by susceptibility results, on patient survival.
  
  
  METHODS
  Patients ≥16 years of age with first episodes of candidaemia during 2001-09 were included. Clinical data were collected retrospectively, including time to appropriate antifungal therapy and patient survival.
  
  
  RESULTS
  The study population included 446 patients [243 (54%) female, mean age 53 years] with candidaemia, 380 (85%) of whom had antifungal susceptibility data. Candida albicans was the most common pathogen (221, 50%) followed by Candida glabrata (99, 22%), Candida parapsilosis (59, 13%), Candida tropicalis (48, 11%) and Candida krusei (6, 1%). Appropriate antifungal therapy consisted of fluconazole (177, 40%), an echinocandin (125, 28%), amphotericin B (41, 9%) and voriconazole (6, 1%); 97 (22%) failed to receive appropriate antifungal therapy. The 30 day mortality was 34% (151/446) and there was no clear relationship between time from positive culture to receipt of appropriate antifungal therapy and 30 day survival. On multivariable Cox regression, increased APACHE II score [hazard ratio (HR) 1.11, 95% CI 1.09-1.13, P<0.001], cirrhosis (HR 2.15, 95% CI 1.48-3.13, P<0.001) and HIV infection (HR 2.03, 95% CI 1.11-3.72, P=0.02) were independent predictors of mortality. A secondary analysis requiring patients in the early treatment group to have received ≥24 h of effective antifungal therapy did show a significant mortality benefit to receiving antifungal treatment within 72 h of a positive blood culture being drawn (30 day mortality for early treatment: 27% versus 40%, P=0.004; HR for mortality with delayed treatment on multivariable analysis: 1.41, 95% CI 1.01-1.98, P=0.045).
  
  
  CONCLUSIONS
  Candida bloodstream infection is associated with high mortality, despite timely receipt of appropriate antifungal therapy.
authors.affiliation: Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL 60612, USA. sgrim@uic.edu
authors.forename: Shellee A
authors.initials: SA
authors.lastname: Grim
authors.forename: Karen
authors.initials: K
authors.lastname: Berger
authors.forename: Christine
authors.initials: C
authors.lastname: Teng
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gupta
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Layden
authors.forename: William M
authors.initials: WM
authors.lastname: Janda
authors.forename: Nina M
authors.initials: NM
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D058387:Candidemia / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents