TABLE 1.
Isolate | Classificationa | Fluconazole MIC (mg/liter) |
Gene mutation(s) |
Relative gene expressionb |
|||||||
---|---|---|---|---|---|---|---|---|---|---|---|
EUCAST guideline | CLSI guideline | ETSD | ETDIR | ERG11 | ERG3 | CDR1 | CDR2 | ERG | MDR | ||
CA-1 | Resistant | 8 | 16 | 12 | 16 | E266D, V488I | V351A, A353T | 1.61 | 2.20 | 1.32 | 1.05 |
CA-2 | Resistant | 8 | 32 | 32 | 32 | A114Sc | V351A | 1.53 | 46.91 | 1.81 | 2.16 |
CA-3 | Resistant | 8 | 8 | 32 | 32 | A114Sc, G464Sc | Wild type | 2.06 | 43.25 | 0.71 | 0.59 |
CA-4 | Resistant | 128 | 256 | 0.125 | 0.125 | D116E, E266D, V488I | H28Y, D219N, S265F, V351A | 1.54 | 10.60 | 2.48 | 4.44 |
CA-5 | Resistant | 128 | 256 | 0.094 | 0.125 | D116E, V481I | H28Y, D219N, S265Y | 0.42 | 4.52 | 0.96 | 0.67 |
CA-6 | Resistant | 128 | 256 | 0.38 | 0.75 | Wild type | Wild type | 0.22 | 3.09 | 0.57 | 0.60 |
CA-7 | Trailer (heavy) | 0.25 | 0.125 | 0.38 | 0.5 | D153E | Wild type | 0.62 | 11.19 | 1.14 | 1.19 |
CA-8 | Trailer (heavy) | 0.125 | 0.125 | 0.25 | 0.5 | D116E, K128T | V351A | 0.42 | 12.59 | 1.37 | 5.57 |
CA-9 | Trailer (heavy) | 0.125 | 0.062 | 0.125 | 0.19 | R246C | V351A | 0.72 | 6.19 | 1.22 | 1.45 |
CA-10 | Trailer (moderate) | 0.25 | 0.25 | 0.38 | 0.5 | D116E, V437I | Wild type | 0.53 | 27.60 | 0.94 | 0.30 |
CA-11 | Trailer (moderate) | 0.25 | 0.25 | 0.75 | 0.75 | Wild type | V351A | 0.53 | 13.40 | 1.51 | 2.54 |
CA-12 | Trailer (moderate) | 0.25 | 0.5 | 0.5 | 0.38 | Wild type | V351A | 0.45 | 2.14 | 1.21 | 4.29 |
CA-13 | Trailer (slightly) | 0.125 | 0.25 | 0.25 | 0.38 | D116E, K128T | N62S | 1.65 | 1.31 | 0.68 | 0.81 |
CA-14 | Trailer (slightly) | 0.125 | 0.062 | 0.125 | 0.19 | D116E, V437I | H28Y | 0.84 | 1.47 | 0.61 | 0.43 |
CA-15 | Trailer (slightly) | 0.25 | 0.25 | 0.75 | 0.75 | Wild type | Wild type | 0.71 | 10.10 | 1.22 | 1.13 |
CA-16 | Trailer (residual) | 0.125 | 0.062 | 0.25 | 0.25 | D116E, V488I, E266D | Wild type | NA | NA | NA | NA |
CA-17 | Trailer (residual) | 0.125 | 0.125 | 0.5 | 0.5 | E266D | V351A | NA | NA | NA | NA |
CA-18 | Trailer (residual) | 0.25 | 0.5 | 1 | 0.5 | E266D, V488I | V351A | NA | NA | NA | NA |
Fluconazole-susceptible isolates (CA-7 to CA-18) were classified according to trailing using a previously reported score: residual trailers, 0.1 to 5%; slight trailers, 6 to 10%; moderate trailers, 11 to 15%; and heavy trailers, >15% (25).
NA, not applicable. Residual trailing isolates were used as controls to determine gene expression.
Mutations previously reported as conferring fluconazole resistance (28).