title: Characterising the post-antifungal effects of micafungin against Candida albicans, Candida glabrata, Candida parapsilosis and Candida krusei isolates.
abstract: In this study, we measured time-kills and post-antifungal effects (PAFEs) for micafungin against Candida albicans (n=4), Candida glabrata (n=3), Candida parapsilosis (n=3) and Candida krusei (n=2) isolates and further characterised the PAFEs. Minimum inhibitory concentrations (MICs) were 0.5-1.0 mg/L against C. parapsilosis and 0.008-0.125 mg/L against the other species. Micafungin caused kills >1 log at 1 x MIC, 4 x MIC (range 1.19-3.10 log) and 16 x MIC (2.27-3.68 log), achieving fungicidal levels (> or = 3 log) against nine isolates. One-hour drug exposure during PAFE experiments resulted in kills of 0.73-2.88 log and 1.72-3.55 log at 4 x and 16 x MIC, respectively, achieving fungicidal levels against five isolates. Isolates of each species collected 8 h after a 1-h exposure to micafungin (4 x and 16 x MIC) were hypersusceptible to sodium dodecyl sulphate (SDS) and Calcofluor White. Cells tested during the PAFE period demonstrated cell wall disturbances as evident on electron micrographs as well as significant reductions in adherence to epithelial cells. Phagocytosis by J774 macrophages was significantly enhanced for three PAFE isolates tested. Micafungin is fungicidal and exerts PAFEs that kill diverse Candida spp., disturb cell walls of viable organisms, reduce adherence and enhance susceptibility to phagocytosis.
authors.affiliation: Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Nguyen
authors.forename: Philip
authors.initials: P
authors.lastname: Ta
authors.forename: Bich Thu
authors.initials: BT
authors.lastname: Hoang
authors.forename: Shaoji
authors.initials: S
authors.lastname: Cheng
authors.forename: Binghua
authors.initials: B
authors.lastname: Hao
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002473:Cell Wall / Q000187:drug effects / Q000648:ultrastructure; D002478:Cells, Cultured; D054714:Echinocandins / Q000494:pharmacology*; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D000077551:Micafungin; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D046529:Microscopy, Electron, Transmission; D010587:Phagocytosis; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D001557:Benzenesulfonates; D054714:Echinocandins; D055666:Lipopeptides; D012967:Sodium Dodecyl Sulfate; C007061:C.I. Fluorescent Brightening Agent 28; D000077551:Micafungin