Article Figures & Data
Figures
- Fig 1
Dose-response relationships for anidulafungin against multiple C. glabrata isolates, including the wild type and fks mutants. Each point represents the mean burden of infection in the kidneys of three neutropenic mice. The dashed line represents the burden of organisms at the start of therapy. Points above the line represent organism growth, whereas points below the line represent organism death (i.e., fungicidal activity).
- Fig 2
Dose-response relationships for caspofungin against multiple C. glabrata isolates, including the wild type and fks mutants. Each point represents the mean burden of infection in the kidneys of three neutropenic mice. The dashed line represents the burden of organisms at the start of therapy. Points above the line represent organism growth, whereas points below the line represent organism death (i.e., fungicidal activity).
- Fig 3
Dose-response relationships for micafungin against multiple C. glabrata isolates, including the wild type and fks mutants. Each point represents the mean burden of infection in the kidneys of three neutropenic mice. The dashed line represents burden of organisms at the start of therapy. Points above the line represent organism growth, whereas points below the line represent organism death (i.e., fungicidal activity).
- Fig 4
Relationship between the free drug 24-h AUC/MIC (AUCf/MIC) and efficacy of anidulafungin (A), caspofungin (B), and micafungin (C) against the wild type and fks mutant C. glabrata isolates. Each symbol represents the mean from three mice. The dashed line represents the burden of organisms at the start of therapy. The sigmoid line is the dose-effect best-fit line and is based on the Hill equation. The PD parameters for Emax, ED50, and the slope of the dose-response line (N) are listed for each drug. R2 is the coefficient of determination.
Tables
- Table 1
In vitro activities of echinocandins against C. glabrata study isolates
C. glabrata strain and isolate no. MIC (mg/liter) fks hot spot mutation In vivo fitnessa Anidulafungin Caspofungin Micafungin Wild-type isolates CG 5592 0.06 0.03 0.02 2.84 CG 513 0.06 0.03 0.02 2.58 CG 33609 0.03 0.03 0.02 2.37 CG 32390 0.06 0.03 0.01 1.29 CG 35315 0.25 0.13 0.06 1.88 CG 5376 0.03 0.03 0.01 2.22 CG 34341 0.13 0.25 0.06 1.81 CG 570 0.03 0.13 NAb 2.45 Mutant fks-1 or fks-2 isolates CG 4747 0.06 1 0.25 Fks2_HS1_L646R 1.97 CG 4720 4 8 4 Fks2_HS1_S645P 2.46 CG 10956 1 2 0.25 Fks2_HS1_F659V 1.01 CG 729 4 16 8 Fks2_HS1_S663P 2.24 CG 14378 2 4 2 Fks1_HS1_S629P 3.17 CG 211 1 1 0.25 Fks2_HS1_S663P 3.11 CG 760 1 1 0.25 Fks2_HS1_S663F 3.22 CG 2092 0.5 1 0.13 Fks1_HS1_L630I 2.90 CG 4742 0.25 1 0.5 Fks2_HS1_L632R 1.92 CG 33616 1 0.25 0.25 2.33 CG 37661 2 0.25 0.25 2.00 - Table 2
In vivo activities of anidulafungin, caspofungin, and micafungin against wild-type C. glabrata isolates in a neutropenic murine disseminated candidiasis model
Antifungal agent and C. glabrata isolate no. MIC (μg/ml) Static dose (mg/kg/24 h) 1-log kill (mg/kg/24 h) AUCf/MIC based on: Static dose 1-log kill Anidulafungin CG 570 0.03 1.97 3.72 12.6 23.8 CG 5592 0.06 3.57 11.8 11.4 37.5 CG 513 0.06 2.45 4.13 7.83 13.2 CG 33609 0.03 2.00 4.21 12.6 26.9 CG 32930 0.06 1.58 3.31 5.00 10.6 CG 35315 0.25 6.40 NAb 4.92 NA CG 5376 0.03 6.80 7.50 40.4 47.7 CG 34341 0.12 6.90 NA 11.0 NA Meana 0.08 3.96 5.78 13.2 26.6 Median 0.06 3.01 4.17 11.2 25.4 SD 0.07 2.35 3.31 11.4 14.2 Caspofungin CG 570 0.12 0.17 0.21 1.39 1.72 CG 5592 0.03 0.12 0.16 3.94 5.25 CG 513 0.03 0.08 0.14 2.62 4.59 CG 33609 0.03 0.06 0.10 1.97 3.28 CG 32930 0.03 0.00 0.02 0.10 0.49 CG 35315 0.12 0.07 1.03 0.57 8.45 CG 5376 0.03 0.17 0.32 5.58 10.5 CG 34341 0.25 0.03 0.86 0.12 3.38 Meana 0.08 0.09 0.35 2.04 4.71 Median 0.03 0.08 0.19 1.68 3.99 SD 0.08 0.06 0.38 1.95 3.35 Micafungin CG 5592 0.02 1.80 5.46 8.40 25.0 CG 513 0.02 1.34 NA 6.20 NA CG 33609 0.02 0.41 1.40 1.90 6.5 CG 32930 0.01 0.29 1.52 2.66 14.2 CG 35315 0.06 2.40 3.77 2.80 4.33 CG 5376 0.01 2.67 4.00 23.0 34.5 CG 34341 0.06 2.18 4.26 2.51 4.9 Meana 0.03 1.58 3.40 6.78 14.9 Median 0.02 1.80 3.89 2.80 10.3 SD 0.02 0.95 1.61 7.54 12.4 - Table 3
In vivo activities of anidulafungin, caspofungin, and micafungin against fks mutant C. glabrata isolates in a neutropenic murine disseminated candidiasis model
Antifungal agent and C. glabrata isolate no. MIC (μg/ml) Static dose (mg/kg/24 h) 1-log kill (mg/kg/24 h) AUCf/MIC based on: Static dose 1-log kill Anidulafungin CG 4747 0.06 1.31 NAa 4.19 NA CG 4720 4 NA NA NA NA CG 10956 1 5.69 NA 1.09 NA CG 729 4 NA NA NA NA CG 14378 2 NA NA NA NA CG 211 1 18.8 NA 3.59 NA CG 760 1 34.9 NA 7.77 NA CG 2092 0.50 3.38 11.2 1.30 4.29 CG 4742 0.25 3.45 17.6 2.65 13.5 CG 33616 1 NA NA NA NA CG 37661 2 NA NA NA NA Meanb 1.53 11.3 14.4 3.43 8.87 Median 1.00 4.57 14.4 3.12 8.87 SD 1.36 13.2 4.53 2.45 6.49 Caspofungin CG 4747 1 0.25 0.43 0.25 0.42 CG 4720 8 14.9 NA 1.06 NA CG 10956 2 2.38 20.3 1.17 5.20 CG 729 16 NA NA NA NA CG 14378 4 NA NA NA NA CG 211 1 4.26 24.8 4.19 11.1 CG 760 1 7.47 52.4 5.81 15.6 CG 2092 1 0.36 0.81 0.36 0.79 CG 4742 1 0.32 2.40 0.31 2.36 CG 33616 0.25 2.08 6.64 8.19 22.1 Meanb 3.53 4.01 15.4 2.67 8.21 Median 1.00 2.23 6.64 1.12 5.20 SD 4.95 5.06 19.0 3.03 8.30 Micafungin CG 4747 0.25 1.12 1.77 0.31 0.49 CG 4720 4 NA NA NA NA CG 10956 0.25 0.22 2.63 0.06 0.73 CG 729 8 NA NA NA NA CG 14378 2 NA NA NA NA CG 211 0.25 4.83 NA 1.33 NA CG 760 0.25 4.24 NA 1.17 NA CG 2092 0.13 0.94 2.65 0.52 1.47 CG 4742 0.50 1.30 10.28 0.18 1.36 CG 33616 0.25 3.88 7.89 1.1 2.2 CG 37661 0.25 9.25 20.60 2.5 5.2 Meanb 1.47 3.22 7.64 0.90 1.91 Median 0.25 2.59 5.27 0.81 1.41 SD 2.47 2.99 7.20 0.81 1.72
