TABLE 2.

In vitro interaction between voriconazole and terbinafine against S. prolificans

Method and strainResult according to theory
LABIa
Nonparametric [median (range)]Parametricb (α ± 95% CI)NonparametricSemiparametricc
FICi-2FICi-1ΣSYN (n)ΣANT (n)ΣSYN (n)ΣANT (n)
SP48
    78980.13 (0.07-0.19)0.10 (0.06-0.28)13.9 ± 1.6700 (29)0 (0)1,118 (51)0 (0)
    79010.25 (0.08-0.75)0.10 (0.05-0.13)10.8 ± 1.8428 (29)0 (0)742 (48)0 (0)
    79060.26 (0.13-0.38)0.13 (0.06-0.25)16.3 ± 4.5457 (26)0 (0)566 (36)0 (0)
    79180.09 (0.04-0.13)0.09 (0.04-0.09)2,479.8 ± 289.1409 (21)0 (0)702 (39)0 (0)
    79020.14 (0.05-0.27)0.09 (0.06-0.13)42.2 ± 7.3709 (44)0 (0)987 (53)0 (0)
        Median0.140.1016.3045707420
SP72
    78980.07 (0.05-0.31)0.14 (0.13-0.75)13.0 ± 3.41,582 (49)0 (0)942 (42)0 (0)
    79010.32 (0.04-0.75)0.13 (0.07-0.25)32.4 ± 6.0195 (14)−3 (1)702 (43)0 (0)
    79060.38 (0.13-0.50)0.28 (0.19-0.38)8.4 ± 3.357 (8)0 (0)67 (4)0 (0)
    79180.08 (0.02-0.28)0.27 (0.16-0.50)1,517.5 ± 334.8770 (29)−9 (2)520 (21)−12 (1)
    79020.29 (0.13-0.31)0.19 (0.08-0.25)6.6 ± 2.1185 (15)0 (0)579 (41)−10 (2)
        Median0.290.1914.0419505790
COL72
    78980.25 (0.02-0.63)0.13 (0.04-0.16)8.9 ± 4.0165 (10)0 (0)442 (20)0 (0)
    79010.75 (0.50-1.00)0.16 (0.13-0.16)29.9 ± 16.80 (0)0 (0)23 (4)0 (0)
    79060.53 (0.07-0.75)0.17 (0.07-0.19)8.0 ± 3.034 (4)0 (0)72 (7)0 (0)
    79180.13 (0.08-0.25)0.20 (0.04-0.31)40.7 ± 16.5254 (8)0 (0)49 (3)0 (0)
    79020.16 (0.08-0.50)0.11 (0.04-0.19)42.0 ± 12.2619 (22)0 (0)903 (32)0 (0)
        Median0.250.1629.901650720
mCOL48
    78980.25 (0.25-0.26)0.25 (0.25-0.50)1,754.9 ± 947.1299 (15)−4 (1)373 (19)−5 (2)
    79010.25 (0.25)0.25 (0.19-0.25)33.7 ± 11.5413 (25)−5 (2)564 (34)0 (0)
    79060.25 (0.25)0.27 (0.25-0.38)2.7 ± 1.5532 (35)0 (0)753 (40)0 (0)
    79180.25 (0.25-0.26)0.13 (0.13-0.25)9.9 ± 4.1214 (10)0 (0)75 (5)0 (0)
    79020.26 (0.25-0.50)0.27 (0.13-0.38)8.2 ± 2.572 (5)0 (0)236 (11)0 (0)
        Median0.250.259.929903730 (0)
mCOL72
    78980.13 (0.08-0.13)0.07 (0.06-0.07)10.3 ± 7.6279 (6)0 (0)56 (3)0 (0)
    79010.25 (0.09-0.38)0.13 (0.07-0.13)5.0 ± 2.6795 (16)0 (0)379 (8)0 (0)
    79060.31 (0.13-0.31)0.13 (0.06-0.13)3.9 ± 2.4566 (180)0 (0)1,072 (26)0 (0)
    79180.13 (0.07-0.13)0.14 (0.07-0.14)4.7 ± 2.9579 (11)0 (0)513 (11)0 (0)
    79020.13 (0.07-0.25)0.09 (0.06-0.13)14.8 ± 5.0464 (9)0 (0)468 (10)0 (0)
        Median0.130.135.056604680
  • a The median absolute coefficient of variation of the differences between observed and predicted percent growth at each drug combination among the replicates of all strains ranged from 41 to 232% (median, 57%) for the SP method, 68 to 166% (median, 123%) for the COL method, and 44 to 83% (median, 53%) for the mCOL method with the semiparametric approach and from 49 to 165% (median, 88%) for the SP method, 86 to 180% (median, 105%) for the COL method, and 45 to 64% (median 51%) for the mCOL method with the nonparametric approach.

  • b The R2 from the nonlinear regression analysis for the fully parametric Greco model ranged from 0.83 to 0.96 (median, 0.90). The IC50s ranged from 0.96 to 2342 mg/liter (geometric mean, 5.9 mg/liter) of terbinafine and from 1.2 to 25 mg/liter (geometric mean, 4.2 mg/liter) of voriconazole. The slope (m) ranged from −0.16 to −1.46 (median, −0.61) for terbinafine and from −0.45 to −1.79 (median, −0.94) for voriconazole.

  • c The R2 from the nonlinear regression analysis for the Emax model of the semiparametric approach ranged from 0.74 to 0.99 (median, 0.90). The IC50s ranged from 1.6 to 67.4 mg/liter (geometric mean, 10.6 mg/liter) of terbinafine and from 0.24 to 16.7 mg/liter (geometric mean, 2.9 mg/liter) of voriconazole. The slopes m ranged from −0.44 to −4.38 (median, −0.92) for terbinafine and from −0.13 to −5.2 (median, −1.2) for voriconazole.