title: Killing rates for caspofungin against Candida albicans after brief and continuous caspofungin exposure in the presence and absence of serum.
abstract: It was previously demonstrated that brief (≤1 h) exposures to echinocandins are as effective to kill Candida albicans cells as continuous 24-h exposure. However, killing rates after continuous and short (1 h) echinocandin exposures to C. albicans have not yet been evaluated in RPMI-1640 with and without 50 % serum. We evaluated four echinocandin susceptible C. albicans bloodstream isolates, ATCC 10231 type strain and an echinocandin-resistant isolate (DPL20, FKS F645P). Caspofungin MICs, time-kill and postantifungal effect (PAFE) tests were performed in RPMI-1640 with and without 50 % serum. Killing rates (k values) in time-kill and PAFE experiments were determined for each strain and concentration. In time-kill experiments, colony count decreases were isolate- and concentration-dependent at 0.25, 1, 4, 8, 16 and 32 mg/L in RPMI-1640, but concentration-independent at 1, 4, 8, 16 and 32 mg/L in 50 % serum. One-hour caspofungin exposure at 4, 16 and 32 mg/L resulted in CFU decreases comparable with the results obtained in time-kill experiments in RPMI-1640, but 50 % serum at 4, 16 and 32 mg/L allowed growth of all isolates (k values were negative) (P < 0.05-0.001). PAFE in 50 % serum decreased markedly at 4, 16 and 32 mg/L. Killing rates remained high and concentration-independent in 50 % serum in case of continuous but not in case of brief caspofungin exposure. As only a short growth inhibition without killing was observed in 50 % serum, clinical relevance of caspofungin PAFE in vivo is questionable.
authors.affiliation: Department of Medical Microbiology, University of Debrecen, Nagyerdei krt. 98, 4032, Debrecen, Hungary.
authors.forename: Renátó
authors.initials: R
authors.lastname: Kovács
authors.forename: Rudolf
authors.initials: R
authors.lastname: Gesztelyi
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
authors.forename: Gábor
authors.initials: G
authors.lastname: Kardos
authors.forename: Marianna
authors.initials: M
authors.lastname: Domán
authors.forename: Réka
authors.initials: R
authors.lastname: Berényi
authors.forename: László
authors.initials: L
authors.lastname: Majoros
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D058387:Candidemia / Q000382:microbiology; D000077336:Caspofungin; D015169:Colony Count, Microbial; D054714:Echinocandins / Q000494:pharmacology*; D006801:Humans; D055666:Lipopeptides; D008297:Male; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects*; D044967:Serum / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin