TABLE 2

In vitro interactions by Bliss independence analysis of ISA in combination with MFG or AMB against different mold isolatesa

Isolate (strain)ISA-MFG Bliss interactionISA-AMB Bliss interaction
Type of interactionbMean %ΔE value (range)Type of interactionMean %ΔE value (range)
Aspergillus fumigatus (4215)SYN29.98 (21.23 to 51.57)ANT−4.64 (−0.84 to −19.72)
Aspergillus flavus (10B)SYN65.59 (19.58 to 128.35)ANT−1.41 (−0.10 to −24.28)
Aspergillus terreus (95644)SYN33.73 (0.74 to 88.11)ANTc−0.04 (−0.01 to −0.25)
SYNc1.35 (0.14 to 4.26)
Fusarium oxysporum species complex (34)ANT−38.57 (−25.95 to −56.34)ANTc−6.45 (−0.89 to −21.2)
SYNc2.69 (2.47 to 3)
Fusarium solani species complex (26)ANTd−17.15 (−5.31 to −29.65)ANT−0.49 (−0.03 to −4.93)
SYNd18.65 (9.72 to 28.11)
Cunninghamella bertholletiae (182)SYN19.31 (4.54 to 35.68)ANTc−0.31(−0.13 to −0.54)
SYNc9.15 (6.39–16.23)
Lichtheimia corymbifera (187)ANTd−15.56 (−6.39 to −25.70)INT
SYNd26.32 (7.43 to 39.74)
Mucor circinelloides (234)INTINT
Rhizopus microsporus (230)INTANT−3.04 (−0.11 to −50.59)
Rhizopus oryzae (98)INTINT
Scedosporium apiospermum (142)ANTd−0.61 (−0.21 to −1.7)SYN11.16 (0.08 to 23.1)
SYNd8.95 (5.22 to 16.46)
  • a ISA, isavuconazole; MFG, micafungin; AMB, amphotericin B deoxycholate.

  • b SYN, synergistic interaction; ANT, antagonistic interaction; INT, indifferent interaction.

  • c The type of ISA-AMB synergy was drug concentration dependent for A. terreus, F. oxysporum, and C. bertholletiae; that is, treatment of A. terreus showed antagonistic interactions at high AMB (1 to 8 mg/liter) and ISA (1 to 16 mg/liter) concentrations, while at low AMB (0.125 to 0.5 mg/liter) and ISA (0.250 to 2 mg/liter) concentrations, the interactions were synergistic. For F. oxysporum, synergistic interactions were noted with a low concentration of ISA (0.0625 mg/liter) and with a range of AMB concentrations (from 0.5 to 4 mg/liter). On the contrary, the combination of high concentrations of ISA (8 to 32 mg/liter) and AMB at a range (from 0.125 to 8 mg/liter) resulted in antagonistic interactions. For C. bertholletiae, low-level synergistic interactions were noted at low concentrations of AMB (0.125 to 0.5 mg/liter) and at high concentrations of ISA (4 to 32 mg/liter), while at higher concentrations of AMB (1 to 8 mg/liter) and ISA (from 2 to 32 mg/liter), the interactions were antagonistic.

  • d The type of ISA-MFG synergy was drug concentration dependent for F. solani, L. corymbifera, and S. apiospermum; that is, treatment of F. solani resulted in antagonistic interactions at low concentrations of ISA (0.03 to 0.125 mg/liter) and in synergistic interactions at high concentrations of ISA (1 to 8 mg/liter), treatment of L. corymbifera resulted in antagonistic interactions at low concentrations of ISA (0.015 to 0.125 mg/liter) and in synergistic interactions at higher ISA concentrations (0.25 to 2 mg/liter), and treatment of S. apiospermum with low concentrations of ISA (0.062 to 0.25 mg/liter) and MFG resulted in synergistic interactions, while treatment with high concentrations of ISA (2 to 32 mg/liter) and MFG resulted in weak antagonistic interactions.