TABLE 1.
MIC50 and MIC ranges for ASP2397 in comparison with amphotericin B, itraconazole, posaconazole, and voriconazole against A. fumigatus with or without CYP51A mutationsa
| Antifungal agent and isolate category | MIC50 (range) (mg/liter) obtained by the specified method |
||||
|---|---|---|---|---|---|
| CLSI | EUCAST | EUCAST—partial inhib. | Modified EUCAST | EUCAST spec-50% | |
| ASP2397 | |||||
| Wild-type isolates | 0.25 (0.06 to 0.25) | 0.5 (0.25 to 1) | 0.25 (0.25 to 0.5) | 0.25 (0.125 to 0.5) | 0.25 (0.25) |
| Cyp51A mutants | 0.125 (0.06 to >4)b | 0.5 (0.125 to >4)c | 0.25 (0.15 to >4)b | 0.25 (0.06 to >4)b | 0.25 (0.06 to >4)b,d |
| Amphotericin B | |||||
| Wild-type isolates | 0.25 (0.125 to 0.25) | 0.25 (0.125 to 0.5) | ND | 0.25 (0.125 to 0.25) | 0.25 (0.125 to 0.5) |
| Cyp51A mutants | 0.25 (0.125 to 1) | 0.25 (0.125 to 1) | ND | 0.25 (0.125 to 1) | 0.25 (0.125 to 1) |
| Itraconazole | |||||
| Wild-type isolates | 0.125 (0.06 to 0.25) | 0.125 (0.125 to 0.25) | ND | 0.125 (0.06 to 0.25) | 0.06 (≤0.03 to 0.125) |
| Cyp51A mutants | 4 (0.5 to >4) | >4 (1 to >4) | ND | >4 (0.5 to >4) | >4 (0.5 to >4) |
| Posaconazole | |||||
| Wild-type isolates | ≤0.03 (≤0.03 to 0.06) | ≤0.03 (≤0.03 to 0.06) | ND | ≤0.03 (≤0.03) | ≤0.03 (≤0.03) |
| Cyp51A mutants | 0.5 (≤0.06 to 4) | 0.5 (0.06 to >4) | ND | 0.5 (0.125 to >4) | 0.25 (≤0.03 to >4) |
| Voriconazole | |||||
| Wild-type isolates | 0.25 (0.25 to 0.5) | 0.5 (0.5 to 1) | ND | 0.25 (0.25 to 0.5) | 0.25 (0.125 to 0.5) |
| Cyp51A mutants | 0.5 (0.125 to 4) | 0.5 (0.25 to >4) | ND | 0.5 (0.125 to 4) | 0.25 (0.125 to 4) |
partial inhib., partial-inhibition endpoint; spec-50%, spectrophotometer reading using a 50% growth inhibition endpoint; ND, not done.
One G54E isolate was found to be resistant (drug MIC of >4 mg/liter) to Asp2397 by all susceptibility tests methods used.
One G54E isolate and one M220K isolate had drug MICs of >4 mg/liter using the full-inhibition endpoint—the drug MIC for the M220K isolate was >4 only using the full-inhibition endpoint (a week of growth at concentrations of 1 to 4 mg/liter) and not using the other methods.
For one isolate, the growth curve crossed the 50% endpoint several times (trailing); thus, an automated endpoint could not be determined.