TABLE 3.

In vitro interaction between miconazole 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 (0.02-0.28)0.04 (0.01-0.05)302.1 ± 32.6173 (15)0 (0)242 (17)0 (0)
    79010.11 (0.02-0.14)0.05 (0.02-0.06)3,072.0 ± 441.7243 (15)0 (0)396 (22)0 (0)
    79020.17 (0.14-0.28)0.08 (0.01-0.28)111.1 ± 17.5163 (20)0 (0)206 (22)−4 (1)
    79060.17 (0.09-0.28)0.04 (0.01-0.13)565.0 ± 110.7160 (11)0 (0)284 (18)0 (0)
    79180.06 (0.03-0.15)0.03 (0.02-0.08)9,462.1 ± 1,194.5460 (33)0 (0)615 (40)0 (0)
        Median0.130.04565.017802840
SP72
    78980.06 (0.02-0.09)0.05 (0.03-0.08)552.1 ± 77.657 (5)0 (0)135 (13)0 (0)
    79010.05 (0.02-0.08)0.05 (0.03-0.06)5,516.6 ± 966.9146 (10)0 (0)365 (21)0 (0)
    79020.06 (0.03-0.28)0.06 (0.03-0.14)1,374.9 ± 242.910 (2)0 (0)78 (8)−6 (1)
    79060.09 (0.03-0.13)0.05 (0.02-0.07)434.5 ± 124.967 (4)0 (0)138 (11)0 (0)
    79180.06 (0.03-0.16)0.05 (0.03-0.27)5,464.7 ± 1,082.9392 (27)0 (0)505 (33)0 (0)
        Median0.060.051,374.96701380
COL72
    78980.06 (0.03-0.09)0.04 (0.02-0.06)817.5 ± 297.57 (1)0 (0)14 (1)0 (0)
    79010.19 (0.06-0.28)0.03 (0.02-0.04)180.1 ± 50.317 (3)0 (0)92 (11)−25 (2)
    79020.05 (0.02-0.08)0.05 (0.02-0.08)128.2 ± 28.48 (1)0 (0)0 (0)0 (0)
    79060.030.05 (0.03-0.16)55.5 ± 23.80 (0)0 (0)0 (0)0 (0)
    79180.08 (0.03-0.19)0.04 (0.02-0.09)633.2 ± 162.257 (3)0 (0)0 (0)0 (0)
        Median0.060.04180.18000
MCOL48
    78980.27 (0.27-0.28)0.05 (0.04-0.13)9.8 ± 2.2556 (49)0 (0)567 (43)−6 (1)
    79010.16 (0.09-0.31)0.05 (0.04-0.05)44.3 ± 11.4955 (55)0 (0)941 (49)0 (0)
    79020.27 (0.27-0.50)0.04 (0.03-0.05)34.1 ± 8.2354 (41)0 (0)392 (35)0 (0)
    79060.38 (0.31-0.51)0.04 (0.04-0.05)18.5 ± 5.0539 (35)0 (0)526 (37)0 (0)
    79180.27 (0.13-0.28)0.31 (0.05-0.31)3,807.5 ± 1,479.4259 (32)0 (0)372 (33)0 (0)
        Median0.270.0534.153905260
MCOL72
    78980.03 (0.03-0.04)0.06 (0.06-0.13)9,505.2 ± 2,824.2487 (30)0 (0)518 (28)−9 (1)
    79010.03 (0.02-0.04)0.09 (0.06-0.09)6,768.1 ± 2,078.91,051 (37)0 (0)1,006 (36)0 (1)
    79020.03 (0.02-0.03)0.06 (0.06-0.13)7,740.3 ± 1,887.31,751 (61)0 (0)1,295 (46)0 (0)
    79060.03 (0.02-0.04)0.13 (0.06-0.13)7,872.5 ± 3,421.3606 (39)0 (0)517 (38)0 (0)
    79180.06 (0.03-0.09)0.08 (0.06-0.08)534.6 ± 141.8595 (45)0 (0)538 (34)0 (0)
        Median0.030.087,740.360605380
  • 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 60 to 124% (median, 95%) for the SP method, 142 to 227% (median, 173%) for the COL method, and 24 to 49% (median, 40%) for the mCOL method with the semiparametric approach and from 69 to 191% (median, 123%) for the SP method, 118 to 343% (median, 236%) for the COL method, and 23 to 56% (median, 36%) for the mCOL method with the nonparametric approach.

  • b The R2 from the nonlinear regression analysis for the fully parametric Greco model ranged from 0.76 to 0.93 (median, 0.88). The IC50s ranged from 0.23 × 103 to −7.2 × 103 mg/liter (geometric mean, 22.1 mg/liter) of terbinafine and from 0.53 to 32.9 mg/liter (geometric mean, 4.2 mg/liter) of miconazole. Relatively high IC50s of terbinafine were obtained after 72 h of incubation. The slope (m) ranged from −0.1 to −0.53 (median, −0.16) for terbinafine and from −0.27 to −4.4 (median, −0.44) for miconazole.

  • c The R2 from the nonlinear regression analysis for the Emax model of the semiparametric approach ranged from 0.73 to 0.99 (median, 0.88). The IC50s ranged from 0.57 to 1,028 mg/liter (geometric mean, 11.4 mg/liter) of terbinafine and from 0.19 to 43.74 mg/liter (geometric mean, 4.43 mg/liter) of miconazole. The slope (m) ranged from −0.10 to −0.86 (median, −0.35) for terbinafine and from −0.24 to −1.63 (median, −0.45) for miconazole.