title: The ever-evolving landscape of candidaemia in patients with acute leukaemia: non-susceptibility to caspofungin and multidrug resistance are associated with increased mortality.
abstract: OBJECTIVE
  The epidemiology and clinical course of candidaemia in patients with acute leukaemia, a population frequently exposed to antifungals, have not been extensively studied. In the present contemporary series of acute leukaemia patients, we describe patient characteristics, Candida species and MIC distributions and investigate the association between antifungal resistance and all-cause mortality.
  
  
  METHODS
  We performed a retrospective review of medical records and microbiological data of adult patients with acute leukaemia or high-risk myelodysplastic syndrome with at least one positive blood culture for Candida species at the MD Anderson Cancer Center between January 2008 and October 2012. Susceptibility was defined according to the 2012 epidemiological cut-off values and clinical breakpoints.
  
  
  RESULTS
  We identified 67 episodes of candidaemia in 65 patients. Almost all episodes (94%) occurred in patients who were receiving antifungal agents, 71% in patients receiving an echinocandin. Almost all isolates (99%) were of non-albicans Candida species [most frequently Candida parapsilosis (32%), Candida tropicalis (23%) and Candida glabrata (20%)]. Caspofungin non-susceptibility was significantly associated with fluconazole resistance (P < 0.001). Non-susceptibility to caspofungin and multidrug resistance were associated with excess 14 day [adjusted HR (aHR) 3.02 (95% CI 1.28-7.09), P = 0.011 and aHR 3.02 (95% CI 1.27-7.14), P = 0.012, respectively] and 30 day [aHR 2.96 (95% CI 1.38-6.37), P = 0.005 and aHR 2.86 (95% CI 1.31-6.21), P = 0.008, respectively] all-cause mortality.
  
  
  CONCLUSIONS
  In patients with acute leukaemia, a shift in candidaemia epidemiology was noted with a 99% predominance of non-albicans species. Non-susceptibility of Candida strains to caspofungin or multidrug resistance were independent markers of poor outcome in this patient population.
authors: Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Emily
authors: E
authors: Wang
authors: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Infectious Disease Section, Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA dfarmakiotis@partners.org.
authors: Dimitrios
authors: D
authors: Farmakiotis
authors: Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Daisy
authors: D
authors: Yang
authors: Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Deborah A
authors: DA
authors: McCue
authors: Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Hagop M
authors: HM
authors: Kantarjian
authors: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Dimitrios P
authors: DP
authors: Kontoyiannis
authors: Department of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Michael S
authors: MS
authors: Mathisen
mesh_terms: D000328:Adult; D000368:Aged; D002175:Candida / Q000145:classification* / Q000187:drug effects* / Q000302:isolation & purification; D058387:Candidemia / Q000453:epidemiology / Q000382:microbiology* / Q000401:mortality*; D000077336:Caspofungin; D026141:Drug Resistance, Multiple, Fungal; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007938:Leukemia / Q000150:complications*; D055666:Lipopeptides; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin
keywords: Candida; MDR; echinocandins