Characterising the post-antifungal effects of micafungin against Candida albicans, Candida glabrata, Candida parapsilosis and Candida krusei isolates.
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.
Nguyen
Katherine T
KT
Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
Ta
Philip
P
Hoang
Bich Thu
BT
Cheng
Shaoji
S
Hao
Binghua
B
Nguyen
M Hong
MH
Clancy
Cornelius J
CJ
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
D000935:Antifungal Agents; D001557:Benzenesulfonates; D054714:Echinocandins; D055666:Lipopeptides; D012967:Sodium Dodecyl Sulfate; C007061:C.I. Fluorescent Brightening Agent 28; D000077551:Micafungin