title: In vitro activity of antifungal combinations against Candida albicans biofilms.
abstract: OBJECTIVE
  The aim of the present study was to evaluate the in vitro activity and synergism of the combinations of amphotericin B/caspofungin and amphotericin B/posaconazole against Candida albicans, grown either as planktonic cells or in biofilms.
  
  
  METHODS
  Ten C. albicans bloodstream isolates used in this study were collected from intensive care patients admitted to the Vienna University Hospital between 2006 and 2007. Chequerboard tests were employed to determine the efficacy of the antifungal combinations amphotericin B/caspofungin and amphotericin B/posaconazole against both planktonic cells and biofilms. C. albicans biofilms were prepared using the static microtitre plate model. The activity of antifungal combination therapy was determined by visual reading for planktonic cells and using the XTT assay for biofilms.
  
  
  RESULTS
  For Candida biofilms the median MIC was 4 mg/L for amphotericin B and caspofungin, and >256 mg/L for posaconazole. The combination amphotericin B/posaconazole yielded synergism [fractional inhibitory concentration index (FICI) <0.26], whereas amphotericin B/caspofungin yielded indifferent interaction only (FICI 0.75-1.25) against all isolates when grown in biofilms. Under planktonic conditions, synergism was demonstrable for the combination amphotericin B/caspofungin against 4 of the 10 isolates, whereas the combination of caspofungin/posaconazole was indifferent against all tested isolates.
  
  
  CONCLUSIONS
  We showed that MICs for planktonic and biofilm forms of C. albicans were much lower when treated with an antifungal combination than when treated with single agents. The combination of amphotericin B/posaconazole yielded synergism against Candida biofilms, whereas amphotericin B/caspofungin yielded indifferent interaction.
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Selma
authors.initials: S
authors.lastname: Tobudic
authors.forename: Christina
authors.initials: C
authors.lastname: Kratzer
authors.forename: Andrea
authors.initials: A
authors.lastname: Lassnigg
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Graninger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Presterl
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001317:Austria; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D000077336:Caspofungin; D004357:Drug Synergism; D054714:Echinocandins / Q000494:pharmacology*; D016469:Fungemia / Q000382:microbiology; D006801:Humans; D007362:Intensive Care Units; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D014230:Triazoles; C101425:posaconazole; D000666:Amphotericin B; D000077336:Caspofungin