Article Figures & Data
Tables
- Table 1.
Selected isolates of Aspergillus spp. used in this study
Species or study isolate no. Source no. Provider (reference no.) A. fumigatus 1 NCPF 7101 (AF210)a, b D. Denning (4, 5) 2 NCPF 7102 (AF294)a, b D. Denning (4) 3 NCPF 7098 (AF71)a, b, c D. Denning (4, 24) 4 NCPF 7097 (AF65)a, b D. Denning (4, 24) 5 NCPF 7100 (AF91)c, d D. Denning (4, 5, 24) 6 NCPF 7099 (AF72)d D. Denning (4, 5) 7 AZ 606e P. Verweij (NAf) 8 NIH 4215d T. Walsh (NA) 9 A 1604a, b A. Espinel-Ingroff (10, 25) A. flavus 10 A 1340a A. Espinel-Ingroff (7) 11 A 830a A. Espinel-Ingroff (7) 12 A 003a, b A. Espinel-Ingroff (7, 10, 25) A. terreus 13 A 122a A. Espinel-Ingroff (7) 14 NIH 961290a T. Walsh (NA) 15 NIH 95644a T. Walsh (NA) ↵a Low itraconazole MICs (≤1.0 μg/ml) by M38-P, Etest, or other methods described in corresponding publication(s).
↵b Animals and patients responded to itraconazole treatment (isolates had low itraconazole MICs [<1.0 μg/ml]).
↵c These two isolates also had either a good (isolate 3) or decreased (isolate 5) response to posaconazole in a murine model.
↵d Animals and patients did not respond to itraconazole treatment (isolates had high itraconazole MICs [>8 μg/ml]).
↵e Voriconazole-resistant laboratory mutant.
↵f NA, not available.
- Table 2.
Interlaboratory agreement on broth microdilution antifungal susceptibility for Aspergillusspp.a
Antifungal agent and MIC criterion % Agreement [all isolates (itraconazole-susceptible isolates)] RPMI RPMI-2% M3 M3-2% Itraconazole MIC-0 90 (92) 92 (94) 90 (91) 85 (85) MIC-2 83 (89) 88 (94) 84 (92) 88 (97) Posaconazole MIC-0 91 (91) 88 (87) 94 (94) 86 (86) MIC-2 96 (96) 95 (96) 93 (99) 91 (96) Ravuconazole MIC-0 93 (95) 87 (85) 94 (95) 88 (89) MIC-2 88 (89) 90 (89) 85 (86) 81 (82) Voriconazole MIC-0 97 (97) 98 (99) 99 (100) 93 (92) MIC-2 88 (96) 94 (95) 90 (92) 96 (96) ↵a Species tested were A. fumigatus ( n = 9 ), A. flavus( n = 3 ), and A. terreus ( n = 3 ); 48-h MICs are shown.
- Table 3.
Itraconazole MICs for Aspergillus spp. in eight laboratoriesa
Isolate(s) (no. tested) and MIC criterion MIC range (MIC90 or modal MIC)b RPMI RPMI-2% M3 M3-2% Itraconazole susceptible (12) MIC-0 0.03–2 (1) 0.03–4 (0.5) 0.06–>8 (1) 0.06–>8 (2) MIC-2 0.01–1 (0.2) <0.008–0.5 (0.12) <0.008–1 (0.2) 0.01–1 (0.2) Itraconazole resistant (isolate no. 5) MIC-0 8–>8 (>8) 8–>8 (>8) 2–>8 (>8) 2–>8 (>8) MIC-2 0.06–>8 (2) 0.06–>8 (1) <0.008–>8 (1) <0.008–>8 (1) Itraconazole resistant (isolate no. 6) MIC-0 1–>8 (>8) 1–>8 (>8) 2–>8 (>8) 1–>8 (>8) MIC-2 0.12–>8 (1) 0.12–>8 (0.5) 1–>8 (1) 0.2–>8 (1) Voriconazole-resistant mutant (1) MIC-0 0.5–>8 (2) 0.5–>8 (0.5) 1–>8 (>8) 1–>8 (>8) MIC-2 0.06–0.5 (0.2) 0.03–0.5 (0.12) 0.06–0.5 (0.2) 0.01–0.2 (0.06) ↵a Species tested were A. fumigatus ( n = 9 ), A. flavus( n = 3 ), and A. terreus ( n = 3 ); see Table 1 for reported data regarding isolates 5 and 6; 48-h MICs are shown.
↵b MICs are reported in micrograms per milliliter; the MIC90 is reported for susceptible isolates and the modal MIC is reported for single resistant isolates.
- Table 4.
Posaconazole (SCH56592) MICs for Aspergillusspp. in eight laboratoriesa
Isolate(s) (no. tested) and MIC criterion MIC range (MIC90 or modal MIC)b RPMI RPMI-2% M3 M3-2% Itraconazole susceptible (12) MIC-0 0.01–0.5 (0.2) 0.03–2 (0.2) 0.03–0.5 (0.2) 0.03–>8 (0.5) MIC-2 0.03–0.12 (0.06) 0.008–0.12 (0.06) 0.008–0.12 (0.06) 0.03–0.06 (0.06) Itraconazole resistant (isolate no. 5) MIC-0 0.2–1 (1) 0.2–2 (0.5) 0.5–2 (0.5) 0.2–2 (0.5) MIC-2 0.03–0.5 (0.2) 0.03–0.2 (0.12) <0.008–0.5 (0.5) <0.008–0.5 (0.2) Itraconazole resistant (isolate no. 6) MIC-0 0.2–1 (0.5) 0.2–1 (0.5) 0.12–2 (1) 0.12–>8 (0.5) MIC-2 0.06–0.5 (0.12) 0.01–0.2 (0.12) 0.01–1 (0.2) 0.03–0.5 (0.2) Voriconazole-resistant mutant MIC-0 0.12–>8 (0.2) 0.06–2 (0.12) 0.5–8 (0.5) 0.12–2 (0.2) MIC-2 0.03–0.12 (0.06) 0.03–1 (0.03) 0.03–0.12 (0.03) 0.03–0.06 (0.03) ↵a Species tested were A. fumigatus ( n = 9 ), A. flavus( n = 3 ), and A. terreus ( n = 3 ); see Table 1 for reported data regarding isolates 5 and 6; 48-h MICs are shown.
↵b MICs are reported in micrograms per milliliter; the MIC90 is reported for susceptible isolates and the model MIC is reported for single resistant isolates.
- Table 5.
Ravuconazole (BMS-207147) MICs for Aspergillusspp. in eight laboratoriesa
Isolate(s) (no. tested) and MIC criterion MIC range (MIC90 or modal MIC)b RPMI RPMI-2% M3 M3-2% Itraconazole susceptible (12) MIC-0 0.12–4 (2) 0.12–>8 (1) 0.2–>8 (4) 0.2–>8 (4) MIC-2 0.01–1 (1) 0.01–0.5 (0.5) 0.01–4 (1) 0.06–1 (1) Itraconazole resistant (isolate no. 5) MIC-0 0.2–0.5 (0.2) 0.12–1 (0.2) 0.2–8 (0.5) 0.12–4 (1) MIC-2 0.01–0.2 (0.12) 0.03–0.12 (0.06) <0.008–0.5 (0.12) 0.008–0.5 (0.06) Itraconazole resistant (isolate no. 6) MIC-0 2–8 (2) 1–>8 (2) 1–>8 (8) 2–>8 (8) MIC-2 0.2–4 (0.5) 0.12–1 (1) 0.2–4 (2) 0.062–8 (2) Voriconazole-resistant mutant (1) MIC-0 2–>8 (4) 1–4 (2) 4–>8 (>8) 2–>8 (8) MIC-2 0.12–4 (1) 0.06–1 (0.5) 0.06–2 (0.5) 0.03–1 (0.2) ↵a Species tested were A. fumigatus ( n = 9 ), A. flavus( n = 3 ), and A. terreus ( n = 3 ); see Table 1 for reported data regarding isolates 5 and 6; 48-h MICs are shown.
↵b MICs are reported in micrograms per milliliter; the MIC90 is reported for susceptible isolates and the modal MIC is reported for single resistant isolates.
- Table 6.
Voriconazole MICs for Aspergillus spp. in eight laboratoriesa
Isolate(s) (no. tested) and MIC criterion MIC range (MIC90 or modal MIC)b RPMI RPMI-2% M3 M3-2% Itraconazole susceptible (12) MIC-0 0.12–2 (1) 0.2–2 (1) 0.5–8 (4) 0.2–>8 (4) MIC-2 0.01–2 (0.5) <0.008–1 (1) <0.008–1 (1) 0.12–1 (0.5) Itraconazole resistant (isolate no. 5) MIC-0 0.2–0.5 (0.2) 0.2–0.5 (0.2) 0.2–2 (0.5) 0.2–1 (0.5) MIC-2 (0.12) 0.03–0.2 (0.12) 0.03–0.2 (0.06) <0.008–0.2 (0.12) 0.03–0.12 (0.12) Itraconazole resistant (isolate no. 6) MIC-0 1–2 (1) 0.5–2 (1) 2–4 (4) 2–8 (2) MIC-2 0.12–0.5 (0.5) 0.12–1 (0.2) 0.5–2 (1) 0.2–1 (0.5) Voriconazole-resistant mutant (1) MIC-0 2–>8 (4) 2–8 (4) 4–>8 (8) 4–>8 (8) MIC-2 0.5–4 (0.5) 0.2–1 (1) 0.2–2 (0.5) 0.2–1 (0.5) - Table 7.
Triazole MIC ranges for the reference A. flavus ATCC 204304 isolate in eight laboratories
Antifungal agent and MIC criterion MIC rangea RPMI RPMI-2% M3 M3-2% Itraconazole MIC-0 0.2–0.5 0.12–0.5 0.5–1 0.5–1 MIC-2b 0.06–0.2 0.06–0.5 0.06–0.2 0.06–0.5 Posaconazole MIC-0 0.06–0.5 0.06–0.5 0.12–0.2 0.12 MIC-2 0.03–0.12 0.03–0.06 0.01–0.12 0.03–0.06 Ravuconazole MIC-0 0.5–4 0.5–2 1–4 0.5–4 MIC-2 0.12–1 0.06–1 0.12–1 0.06–2 Voriconazole MIC-0 0.5–4 0.5–2 0.5–>8 0.5–4 MIC-2 0.12–0.5 0.06–0.5 0.12–1 0.12–2