DOI: 10.1128/AAC.47.7.2100-2107.2003
Article Figures & Data
Tables
- TABLE 1.
Effects of variations in medium and inoculum on control OD and caspofungin MIC data for eight isolates each of Candida spp. and A. fumigatusa
Medium pH Inoculum (CFU/ml) Mean ± SD control OD No. of isolates for which ODs were <0.150 IC50 (μg/ml) IC80 (μg/ml) Candida spp. A. fumigatus Candida spp. A. fumigatus Candida spp. A. fumigatus Candida spp. A. fumigatus Range Gmeanb Range Gmean Range Gmean Range Gmean AM3 5.0 2 × 103 0.339 ± 0.115 1.165 ± 0.224 0 0 0.016-4.0 0.23 0.063-0.25 0.19 0.063-4.0 0.33 0.25-4.0 0.59 2 × 104 0.326 ± 0.050 1.279 ± 0.256 0 0 0.063-4.0 0.33 0.016-0.25 0.11 0.063->16 1.01 0.063-16 1.20 2 × 105 0.393 ± 0.064 0 0.063-4.0 0.55 0.063->16 0.93 7.0 2 × 103 0.215 ± 0.054 0.903 ± 0.312 1 0 0.063-2.0 0.28 0.13-1.0 0.20 0.063-2.0 0.41 0.13->32 1.10 2 × 104 0.276 ± 0.049 1.244 ± 0.312 0 0 0.016-2.0 0.28 0.016-0.13 0.059 0.063-2.0 0.39 0.016-16 0.78 2 × 105 0.330 ± 0.077 0 0.016-4.0 0.33 ≤0.032-4.0 0.39 MH 7.0 2 × 103 0.249 ± 0.061 1.686 ± 0.441 0 0 0.016-4.0 0.35 0.063-0.25 0.16 0.25-4.0 0.59 0.13-0.5 0.27 2 × 104 0.278 ± 0.055 1.519 ± 0.571 0 0 0.13-4.0 0.47 0.016-0.25 0.12 0.25-4.0 0.77 0.13-1.0 0.28 2 × 105 0.488 ± 0.369 0 0.063-4.0 0.60 0.063-4.0 0.60 RPMI 1640 5.0 2 × 103 0.673 ± 0.208 0.033 ± 0.024 0 8 0.25->16 1.4 0.25->16 2.38 2 × 104 0.819 ± 0.165 0.058 ± 0.073 0 7 0.25->16 2.0 0.5->16 5.66 2 × 105 0.851 ± 0.154 0 0.25->16 2.4 0.25->16 4.00 7.0 2 × 103 0.782 ± 0.135 0.243 ± 0.083 0 0 0.25-8.0 1.2 0.25->16 1.41 0.25-8.0 1.54 1->16 13.5 2 × 104 0.892 ± 0.116 0.313 ± 0.131 0 1 0.25-16 1.7 0.13-1.0 0.46 0.5->16 4.00 2->16 19.5 2 × 105 0.915 ± 0.084 0 0.25-16 1.4 0.25->16 2.00 SAB 5.2 2 × 103 1.185 ± 0.278 3.188 ± 0.396 0 0 0.063-2.0 0.25 0.13-1.0 0.39 0.13-8.0 0.55 0.25-2.0 0.65 2 × 104 1.325 ± 0.090 3.263 ± 0.095 0 0 0.063-2.0 0.36 0.13-0.25 0.19 0.13-16 0.93 0.25-0.5 0.28 2 × 105 1.295 ± 0.096 0 0.13-16 1.0 0.13 0.13-16 1.01 - TABLE 2.
Ranges of caspofungin IC50 and IC80s for eight isolates each of Candida spp. and A. fumigatus determined in six different media and with two or three different starting fungus concentrationsa.
Isolate Range IC50 (μg/ml) No. of dilnsb Mode IC50 (μg/ml) Range IC80 (μg/ml) No. of dilns Mode IC80 (μg/ml) C. krusei ATCC 6258 0.016-2.0 7 0.25 0.063-2.0 5 0.25 C. parapsilosis ATCC 22019 0.25-2.0 3 0.50 0.25->16 7 0.50 C. albicans B59630 ≤0.032-0.50 5 0.063 ≤0.032->16 11 0.063 C. albicans J990578 0.063->16 9 0.25 0.25->16 7 0.25 C. albicans NR2 0.25-4.0 4 0.50 0.5->16 6 0.50 C. albicans NR3 1.0-8.0 3 4.0 2->16 4 2.0 C. albicans T25 2.0->16 4 4.0 2->16 4 4.0 C. glabrata J981216 0.063-1.0 4 0.13 0.063-1.0 4 0.13 A. fumigatus J980659 0.063-1.0 4 0.25 0.5->16 6 0.50 A. fumigatus J980561 0.063-0.50 3 0.25 0.13-2.0 4 0.25 A. fumigatus J970398 ≤0.032->16 11 0.13 0.13->16 8 0.25 A. fumigatus J970377 0.063-2.0 5 0.25 0.25->16 7 >16 A. fumigatus J960180 0.016-0.25 4 0.016 ≤0.032-1.0 6 0.25 A. fumigatus J960330 0.13-0.50 2 0.13 0.13->16 8 0.25 A. fumigatus J940362 ≤0.032-1.0 6 0.25 0.13->16 8 0.25 A. fumigatus J931199 0.063->16 9 0.13 0.25->16 7 0.25 - TABLE 3.
Multivariate analysis of effects of performance variables on control growth OD and MIC (IC50 and IC80) for 13 isolates of Candida spp. and 8 isolates of A. fumigatus
Isolate Control OD No. of isolates for which OD was <0.100 Significant variablesa IC50 (μg/ml) Significant variable(s)a IC80 (μg/ml) Significant variable(s)a Range Median Range Gmeanb Range Gmean C. albicans B59630 0.279-1.558 0.629 0 M, G 0.016-16 0.096 M, G 0.016->16 2.5 G C. albicans J981364 0.422-1.555 0.923 0 G, T 0.063->16 0.24 M, G 0.063->16 2.6 G C. albicans J981371 0.461-1.569 0.909 0 G, T ≤0.032->16 0.24 M, G, I 0.063->16 4.6 M, G C. albicans J990578 0.391-1.472 0.701 0 M, G 0.063->16 0.77 G, I, H ≤0.016->16 9.7 G, I C. albicans NR2 0.220-1.536 0.563 0 M, G 0.13->16 2.2 M, I, T 0.13->16 8.4 M, G, T C. albicans NR3 0.218-1.544 0.528 0 M, G 1.0->16 3.5 M, G, I, T 1.0->16 9.0 G, T C. albicans NR4 0.343-1.514 0.813 0 M, G 0.063->16 2.4 M, G, I, T 0.50->16 7.3 G, T C. albicans T25 0.272-1.429 0.556 0 M, G 2.0->16 9.3 M, I, T, H 4.0->16 17 M, G C. albicans T26 0.315-1.433 0.668 0 M, G, I 2.0->16 8.4 M, I, T, H 2.0->16 16 G, I, T C. albicans T28 0.346-1.385 0.614 0 M, G 0.063->16 0.55 M, I, H 0.25->16 7.8 G, I, H C. albicans T32 0.369-1.459 0.752 0 M, G ≤0.032->16 0.51 M, G, H 0.063->16 6.0 M, G C. glabrata J981216 0.210-1.714 0.726 0 M, G 0.063-0.50 0.16 M, G 0.063-1.0 0.28 M, G C. krusei ATCC 6258 0.163-1.676 0.520 0 M, G, H 0.13-1.0 0.25 M, I, H 0.13->16 0.90 M, G C. parapsilosis ATCC 22019 0.195-1.447 0.471 0 M, G, H 0.13-2.0 0.44 M, G, I, H 0.25->16 2.9 G, T A. fumigatus J931199 0.105-3.748 0.817 0 T, H 0.063->16 0.8 I, H 0.13->16 5.7 M A. fumigatus J940362 0.087-3.990 0.809 5 T, H 0.063->16 0.8 T, H 0.13->16 5.6 M A. fumigatus J960180 0.101-3.990 0.937 0 T, H ≤0.032->16 1.0 T, H 0.13->16 4.6 M A. fumigatus J960330 0.085-3.644 0.552 6 T, H ≤0.032->16 1.3 M, H 0.063->16 5.5 M A. fumigatus J970377 0.103-3.990 0.737 0 M, T, H ≤0.032->16 1.3 M, H 0.13->16 6.6 M, T A. fumigatus J970398 0.089-3.304 0.582 3 T, H ≤0.032->16 1.5 M, H 0.13->16 5.8 M A. fumigatus J980561 0.033-3.990 0.553 7 T, H ≤0.032->16 0.9 H 0.13->16 4.1 M A. fumigatus J980659 0.106-3.976 0.783 0 G, T, H 0.13->16 1.3 T, H 0.13->16 7.3 M ↵ a G, glucose concentration; I, initial cell concentration; M, growth medium; S, plates sealed with sticker; T, incubation temperature; H, incubation time. For inclusion in the table, the variable must have been shown to be a significant contributor to OD or MIC variation by ANOVA at the level of P < 0.01.
↵ b Gmean, geometric mean.
- TABLE 4.
IC50s and IC80s of caspofungin for 22 fungal isolates in AM3 medium from three different suppliersa
Isolate AM3 from Difco AM3 from Oxoid AM3 from VWR 48 h 72 h 48 h 72 h 48 h 72 h IC50 (μg/ml) IC80 (μg/ml) IC50 (μg/ml) IC80 (μg/ml) IC50 (μg/ml) IC80 (μg/ml) IC50 (μg/ml) IC80 (μg/ml) IC50 (μg/ml) IC80 (μg/ml) IC50 (μg/ml) IC80 (μg/ml) C. albicans B59630 0.5 0.5 1 1 0.5 1 1 1 0.5 0.5 0.5 1 C. albicans J981309 0.5 0.5 0.5 0.5 0.5 0.5 1 1 0.5 0.5 0.5 0.5 C. albicans J981364 0.5 0.5 0.5 0.5 0.5 0.5 1 1 0.5 0.5 0.5 1 C. albicans J981371 0.5 >16 0.5 0.5 0.5 1 0.5 1 0.5 0.5 1 2 C. albicans J990578 0.5 >16 1 1 0.5 0.5 1 2 1 1 1 1 C. albicans NR2 2 4 2 4 2 2 4 4 4 8 2 8 C. albicans NR3 4 4 4 8 2 4 4 4 2 4 4 >16 C. albicans T25 8 8 8 8 4 4 4 4 4 8 8 8 C. albicans T26 8 8 4 8 4 4 1 4 4 8 4 8 C. albicans T28 >16 >16 2 2 0.5 0.5 0.5 0.5 0.5 0.5 0.5 2 C. albicans T32 >16 >16 1 1 1 1 1 1 0.5 0.5 1 1 C. glabrata J981216 0.5 0.5 0.5 1 0.5 0.5 1 1 0.5 0.5 2 2 C. krusei ATCC 6258 0.5 0.5 0.5 1 0.5 1 1 1 1 1 1 1 C. parapsilosis ATCC 22019 1 1 1 1 1 1 1 2 1 1 1 1 A. fumigatus J931199 0.5 8 1 8 1 4 1 2 1 4 1 8 A. fumigatus J940362 1 2 1 4 2 4 1 8 1 2 4 4 A. fumigatus J960180 0.5 4 1 8 1 1 1 2 0.5 8 2 >16 A. fumigatus J960330 0.5 8 1 2 0.5 1 1 4 1 1 1 1 A. fumigatus J970377 1 16 1 >16 1 >16 1 >16 1 2 16 >16 A. fumigatus J970398 0.5 1 1 1 1 1 1 2 0.5 1 1 1 A. fumigatus J980561 0.5 2 0.5 1 1 1 1 2 1 1 1 1 A. fumigatus J980659/3 1 >16 1 >16 0.5 >16 1 >16 1 1 1 >16 ↵ a The endpoints were read after 48 and 72 h of incubation.
