Abstract
Micafungin is an effective antifungal agent useful for the therapy of invasive candidiasis. Candida albicans is the most common cause of invasive candidiasis; however, infections due to non-C. albicans species, such as Candida parapsilosis, are rising. Killing and postantifungal effects (PAFE) are important factors in both dose interval choice and infection outcome. The aim of this study was to determinate the micafungin PAFE against 7 C. albicans strains, 5 Candida dubliniensis, 2 Candida Africana, 3 C. parapsilosis, 2 Candida metapsilosis and 2 Candida orthopsilosis. For PAFE studies, cells were exposed to micafungin for 1 h at concentrations ranging from 0.12 to 8 μg/ml. Time-kill experiments (TK) were conducted at the same concentrations. Samples were removed at each time point (0-48 h) and viable counts determined. Micafungin (2 μg/ml) was fungicidal (≥ 3 log10 reduction) in TK against 5 out of 14 (36%) strains of C. albicans complex. In PAFE experiments, fungicidal endpoint was achieved against 2 out of 14 strains (14%). In TK against C. parapsilosis, 8 μg/ml of micafungin turned out to be fungicidal against 4 out 7 (57%) strains. Conversely, fungicidal endpoint was not achieved in PAFE studies. PAFE results for C. albicans complex (41.83 ± 2.18 h) differed from C. parapsilosis complex (8.07 ± 4.2 h) at the highest tested concentration of micafungin. In conclusion, micafungin showed significant differences in PAFE against C. albicans and C. parapsilosis complexes, being PAFE for the C. albicans complex longer than for the C. parapsilosis complex.
Highlights
Invasive candidiasis is a leading cause of mortality worldwide, being Candida albicans the predominant cause of candidemia and invasive candidiasis
A total of 21 Candida strains were selected for testing: 14 strains from the C. albicans complex (C. albicans: 5 blood isolates [Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU) 99–101, 99–102, 99–103, 99–104 and 99–105] and 2 reference strains [NCPF 3153 and 3156]; C. dubliniensis: 4 blood isolates [UPV/EHU 00–131, 00–132, 00–133, 00–135] and 1 reference strain [NCPF 3949]; C. africana: 1 vaginal isolate [UPV/EHU 97–135] and 1 reference strain [ATCC 2669]) and 7 strains from the C. parapsilosis complex (C. parapsilosis sensu stricto: 1 blood isolate [UPV/EHU 09–378] and 2 reference strains [ATCC 22019 and ATCC 90018]; C. metapsilosis: 1 blood isolate [UPV/EHU 07–045] and 1 reference strain [ATCC 96143]; C. orthopsilosis: 1 blood isolate [UPV/EHU 07–035] and 1 reference strain [ATCC 96139])
Micafungin showed prolonged postantifungal effects (PAFE) ( 37.5 h) against all strains of C. albicans complex with 2 μg/ml (p < 0.0001)
Summary
Invasive candidiasis is a leading cause of mortality worldwide, being Candida albicans the predominant cause of candidemia and invasive candidiasis. Candidiasis due to non-C. albicans species, such as Candida parapsilosis, Candida glabrata, Candida tropicalis, Candida krusei, Candida lusitaniae, Candida guilliermondii, are increasing. Investigación Sanitaria (FIS PI11/00203), and UPV/ EHU (UFI 11/25)
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