title: Candidacidal effect of fluconazole and chlorhexidine released from acrylic polymer.
abstract: OBJECTIVE
  To investigate the efficacy and rate of killing of a fluconazole- or chlorhexidine-impregnated polymeric delivery system against fluconazole-susceptible and -resistant Candida albicans and fluconazole-resistant Candida glabrata.
  
  
  METHODS
  Poly(ethyl methacrylate)/tetrahydrofurfuryl methacrylate (PEM/THFM) discs impregnated with chlorhexidine, pure fluconazole (FLCp) or fluconazole from capsules (FLCc) were prepared by substituting a portion of PEM powder with an equivalent amount of each drug. Discs were incubated in sterile water for 1, 3, 7, 14, 21 and 28 days. The amounts of drugs in the leachates were measured spectrophotometrically and their antifungal activity against fluconazole-susceptible (n=1) and fluconazole-resistant (n=2) candidal isolates was determined using a time-kill method and by comparing the released concentrations with the corresponding MICs.
  
  
  RESULTS
  Fluconazole and chlorhexidine leached from PEM/THFM polymer for up to 28 days and the released concentrations were fungicidal against all three Candida isolates for at least the first 7 days. Chlorhexidine leachates killed all Candida isolates more rapidly than the two fluconazole formulation leachates throughout the study period. FLCc leachates required longer incubation for 100% killing than FLCp leachates. The proportion of viable C. glabrata dropped more slowly than that of C. albicans with the same MIC.
  
  
  CONCLUSIONS
  The concentrations of chlorhexidine and fluconazole leached from the PEM/THFM polymer were fungicidal against all Candida isolates, including those resistant to fluconazole, for the first 7 days. Chlorhexidine leachates showed a rapid fungicidal activity for up to 4 weeks, which can be of use in cases with poor response to conventional antifungals.
authors.affiliation: School of Dentistry,  University of Manchester, Higher Cambridge Street, Manchester M15 6FH,  UK.
authors.forename: N
authors.initials: N
authors.lastname: Salim
authors.forename: C
authors.initials: C
authors.lastname: Moore
authors.forename: N
authors.initials: N
authors.lastname: Silikas
authors.forename: J
authors.initials: J
authors.lastname: Satterthwaite
authors.forename: R
authors.initials: R
authors.lastname: Rautemaa
mesh_terms: D000180:Acrylic Resins / Q000378:metabolism*; D002176:Candida albicans / Q000187:drug effects*; D041221:Candida glabrata / Q000187:drug effects*; D002710:Chlorhexidine / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers / Q000378:metabolism; D015725:Fluconazole / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; C006903:carbopol 940; D015725:Fluconazole; D002710:Chlorhexidine