TABLE 1.
Drug in combination and strain | Median MIC (range) of drug (μg/ml)
|
|||
---|---|---|---|---|
Alone
|
In combination
|
|||
Azole | FK506 | Azole | FK506 | |
FLC | ||||
Susceptible | ||||
CA5 | 0.25 (0.25-0.5) | 512 | 0.25 (0.125-0.5) | 0.002 (0.002) |
CA8 | 0.25 (0.125-0.5) | 512 | 0.125 (0.125-0.25) | 0.002 (0.002) |
CA12 | 4 (2-4) | 512 | 2 (1-2) | 0.008 (0.004-0.008) |
CA14 | 0.5 (0.25-0.5) | 512 | 0.25 (0.25-1) | 0.002 (0.002-0.004) |
CA129 | 0.5 (0.5-1) | 512 | 0.25 (0.25-0.5) | 0.008 (0.004-0.016) |
Resistant | ||||
CA10 | 256 (256-512) | 512 | 0.25 (0.125-0.5) | 0.063 (0.016-0.125) |
CA15 | 128 (64-128) | 512 | 0.5 (0.25-0.5) | 0.008 (0.004-0.016) |
CA16 | 64 (64-128) | 512 | 0.5 (0.25-2) | 0.008 (0.008-0.016) |
CA135 | 64 (64-128) | 512 | 0.25 (0.125-0.5) | 0.004 (0.004-0.008) |
CA137 | 64 (64-128) | 512 | 0.5 (0.25-0.5) | 0.002 (0.002-0.008) |
ITR | ||||
Susceptible | ||||
CA5 | 0.031 (0.031-0.063) | 512 | 0.031 (0.031-0.063) | 0.063 (0.016-0.063) |
CA8 | 0.016 (0.008-0.031) | 512 | 0.008 (0.008-0.016) | 0.002 (0.002) |
CA12 | 0.063 (0.063-0.125) | 512 | 0.031 (0.031-0.063) | 0.125 (0.063-0.125) |
CA14 | 0.063 (0.031-0.125) | 512 | 0.031 (0.031-0.125) | 0.002 (0.002) |
CA129 | 0.063 (0.063-0.125) | 512 | 0.031 (0.031-0.063) | 0.063 (0.063-0.125) |
Resistant | ||||
CA10 | 128 (64-128) | 512 | 0.031 (0.031-0.063) | 0.125 (0.063-0.125) |
CA15 | 32 (16-64) | 512 | 0.063 (0.031-0.125) | 0.063 (0.031-0.125) |
CA16 | 32 (16-64) | 512 | 0.016 (0.008-0.031) | 0.125 (0.125) |
CA135 | 16 (16-32) | 512 | 0.016 (0.016-0.031) | 0.063 (0.031-0.125) |
CA137 | 16 (16-32) | 512 | 0.063 (0.031-0.063) | 0.008 (0.008-0.031) |
VRC | ||||
Susceptible | ||||
CA5 | 0.016 (0.016-0.031) | 512 | 0.016 (0.016-0.031) | 0.002 (0.002) |
CA8 | 0.008 (0.008-0.016) | 512 | 0.016 (0.008-0.031) | 0.002 (0.002) |
CA12 | 0.031 (0.008-0.031) | 512 | 0.016 (0.008-0.031) | 0.008 (0.004-0.016) |
CA14 | 0.008 (0.004-0.016) | 512 | 0.008 (0.008) | 0.002 (0.002) |
CA129 | 0.016 (0.016-0.031) | 512 | 0.008 (0.008-0.016) | 0.008 (0.008-0.125) |
Resistant | ||||
CA10 | 64 (32-64) | 512 | 0.008 (0.008-0.016) | 0.063 (0.031-0.063) |
CA15 | 8 (4-16) | 512 | 0.008 (0.008-0.016) | 0.125 (0.063-0.125) |
CA16 | 8 (4-8) | 512 | 0.008 (0.008-0.016) | 0.031 (0.031-0.063) |
CA135 | 8 (4-8) | 512 | 0.016 (0.008-0.031) | 0.031 (0.016-0.063) |
CA137 | 8 (4-16) | 512 | 0.008 (0.008-0.016) | 0.016 (0.008-0.016) |
Strains were categorized as susceptible or resistant according to the interpretive breakpoints of CLSI criteria for FLC (≤8 and ≥64 μg/ml, respectively), ITR (≤0.1 and ≥1 μg/ml, respectively), and VRC (≤1 and ≥4 μg/ml, respectively) (11). For azole-susceptible isolates, when drugs were used in combination, MICs of azoles showed no apparent changes, while for azole-resistant strains, MICs of azoles decreased markedly when drugs were used in combination.