Comparison of killing activity of caspofungin against Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis (original) (raw)
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Journal of Antimicrobial Chemotherapy, 2008
We evaluated the in vitro activity of caspofungin against Candida dubliniensis strains using MIC and minimum fungicidal concentration (MFC) measurements and time-kill methodology. Methods: We used six C. dubliniensis clinical isolates and the CD 36 type strain. MICs and MFCs of caspofungin were determined using the standard broth microdilution method with normal (10 3 cells/mL) and elevated (10 5 cells/mL) starting inocula in RPMI-1640 and antibiotic medium 3 (AM3). MIC was determined after 24 h, and plating for MFC determination was performed after 48 h. In time-kill tests, all strains were tested at 0.06-16 mg/L caspofungin concentrations in RPMI-1640 and AM3. Results: In RPMI-1640, the MIC range was 0.06-8 mg/L. Trailing growth was observed regardless of the starting inoculum after 48 h, but not after 24 h. In AM3 regardless of starting inoculum, MICs were 0.03 mg/L. After 48 h, trailing was not detected; two isolates grew at a concentration of 8 mg/L using 10 5 cells/mL as the starting inoculum [ paradoxical growth (PG)]. All MFCs in RPMI-1640 and AM3 were >8 and 0.12 mg/L, respectively. In AM3, all but a single isolate showed PG in the MFC tests. Time-kill tests confirmed the results obtained by MFC tests both in RPMI-1640 and AM3. Conclusions: In vitro activity of caspofungin against C. dubliniensis depended on the starting inoculum and medium used. Using AM3 eliminated trailing from MIC determinations but not PG in MIC, MFC and time-kill tests.
International Journal of Antimicrobial Agents, 2016
The in vitro activity of caspofungin and micafungin was determined with and without farnesol in RPMI-1640 against Candida parapsilosis biofilms. Drug interactions were examined using the XTT colorimetric assay-based broth microdilution checkerboard method. Drug-drug interactions were assessed utilizing a fractional inhibitory concentration index (FICI), Bliss independence and a comparison of time-kill curves. The median sessile MICs of five C. parapsilosis clinical isolates ranged between 32-256 mg/L, 16-512 mg/L and >300 µM for caspofungin, micafungin and farnesol, respectively. The median MICs for caspofungin and micafungin in combination with farnesol showed 8-64-and 4-64-fold decrease, respectively. Paradoxical growth noticed with both echinocandins was eliminated by farnesol. Based on FICIs, synergism was observed for caspofungin (range of median FICIs: 0.155-0.5) and micafungin (range of median FICIs: 0.093-0.5). Concordantly, MacSynergy analysis and global fitting of nonlinear regression based on a Bliss independence model showed synergism for caspofungin and micafungin, as well. In line with FICI findings and the Bliss independence model, synergistic interactions were confirmed by time-kill experiments. The metabolic activity of fungal cells was significantly inhibited by caspofungin+farnesol at all three tested combinations (4mg/L+75µM, 8mg/L+75µM, 16mg/L+75µM) between 3-24 hours compared with control (P<0.05-0.001). Significant inhibition was observed for micafungin+farnesol between 3-12 hours (P<0.001) but not at 24 hours. Despite the favorable effect of farnesol in combination with echinocandins, further in vivo studies are needed to confirm its therapeutic advantage in catheter-associated infections caused by C. parapsilosis.
Effects of Caspofungin against Candida guilliermondii and Candida parapsilosis
Antimicrobial Agents and Chemotherapy, 2006
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Clinical Microbiology and Infection, 2009
Recent studies suggest that differences in antifungal activity among echinocandins may exist. In this study, the activities of three echinocandins (anidulafungin, caspofungin, and micafungin) against Candida parapsilosis isolates from burn unit patients, healthcare workers and the hospital environment were determined. Additionally, the effect of these echinocandins on the cell morphology of caspofungin-susceptible and caspofungin-non-susceptible isolates was assessed using scanning electron microscopy (SEM). The C. parapsilosis isolates obtained from patients were susceptible to anidulafungin, but were less so to caspofungin and micafungin. Isolates obtained from healthcare workers or environmental sources were susceptible to all antifungals. SEM data demonstrated that although anidulafungin and caspofungin were equally active against a caspofungin-susceptible C. parapsilosis strain, they differed in their ability to damage a caspofungin-non-susceptible strain, for which lower concentrations of anidulafungin (1 mg/L) than of caspofungin (16 mg/L) were needed to induce cellular damage and distortion of the cellular morphology. To determine whether the difference in the antifungal susceptibility of C. parapsilosis isolates to anidulafungin as compared to the other two echinocandins could be due to different mutations in the FKS1 gene, the sequences of the 493-bp region of this gene associated with echinocandin resistance were compared. No differences in the corresponding amino acid sequences were observed, indicating that differences in activity between anidulafungin and the other echinocandins are not related to mutations in this region. The results of this study provide evidence that differences exist between the activities of anidulafungin and the other echinocandins.
Diagnostic Microbiology and Infectious Disease, 2009
Killing activity of amphotericin B, fluconazole, voriconazole, posaconazole, and 5-fluorocytosine was determined against 6 Candida parapsilosis, 3 Candida orthopsilosis, and 4 Candida metapsilosis clinical isolates. After 24 h, 1 of 6 C. parapsilosis, 1 of 3 C. orthopsilosis, and 3 of 4 C. metapsilosis isolates were killed at 1 to 4 μg/mL (1-8× MIC) amphotericin B. The remaining isolates were killed by 2 to 4 μg/mL amphotericin B after 48 h. Fluconazole was fungistatic at ≥1× MIC (0.5-2 μg/mL) against C. parapsilosis and at ≥2× MIC (4-8 μg/mL) against C. orthopsilosis and C. metapsilosis isolates. Voriconazole inhibited C. parapsilosis at ≥1× MIC (0.015-0.12 μg/mL), but the other 2 species were inhibited only at 4 to 8× MIC (0.25-0.5 μg/mL). Against C. orthopsilosis and C. metapsilosis, posaconazole was fungistatic close to the MIC (0.03-0.06 and 0.015-0.03 μg/mL, respectively). Against C. orthopsilosis and C. metapsilosis, fluconazole and voriconazole, but not posaconazole, seem to be less active in vitro than against C. parapsilosis.
Mycopathologia, 2014
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 c...