TABLE 2.
Association of azole/fluconazole exposure with the emergence of fluconazole-tolerant and/or azole non-susceptible C. tropicalis blood isolates. Patients infected with isolates showing fluconazole tolerance <50% were not included as their clinical data were not available.
| Minimum inhibitory concentration (μg/ml) |
||||||||||
| Patient # | Isolate # | FLC | VORI | ITRA | POSA | ISA | Azole prophylaxis | Azole as main treatment | Azole therapeutic failure | Outcome |
| Azole non-susceptible isolates (n = 20) | ||||||||||
| P1 | 28 | 0.25 | 0.032 | 0.125 | ≥16 | 0.5 | None | Yes | FLC failure* | Died |
| P2 | 29 | ≥ 64 | 8 | ≥16 | 16 | 2 | FLC | No (changed to AMB and CASP) | FLC failure | Died |
| P3 | 30 | 64 | 2 | 0.5 | 0.064 | 0.25 | FLC | Yes (VORI changed to CASP) | FLC + VORI failure | Died |
| P4 | 82 | ≥64 | ≥16 | ≥16 | ≥16 | 4 | None | Yes (FLC changed to CASP) | FLC failure | Alive |
| 83 | ≥64 | ≥16 | ≥16 | ≥16 | 4 | |||||
| P5 | 172 | ≥64 | 0.125 | 0.064 | 2 | 0.125 | None | Yes | No | Alive |
| P6 | 27 | 2 | 0.032 | 4 | ≥16 | 2 | None | NO (ANI) | Azole-naïve | Alive |
| P7 | 31 | 32 | 1 | 0.5 | 0.125 | 0.032 | None | NO (MICA) | Azole-naïve | Alive |
| P8 | 57 | 8 | ≥16 | ≥16 | 1 | 1 | None | No (ANI) | Azole-naïve | Alive |
| 58 | ≥64 | 16 | ≥16 | ≥16 | 8 | |||||
| P9 | 69 | 1 | 0.032 | 0.5 | 4 | ≥16 | None | No (MICA) | Azole-naïve | Died |
| P10 | 70 | ≥64 | ≥16 | ≥16 | 2 | 4 | None | No (CASP, MICA, ANI, AMB) | Azole-naïve | Died |
| P11 | 77 | ≥64 | ≥16 | 4 | ≥16 | 1 | None | No (CASP) | Azole-naïve | Died |
| 78 | ≥64 | ≥16 | 4 | ≥16 | 1 | |||||
| 79 | ≥64 | ≥16 | 4 | ≥16 | 1 | |||||
| 80 | ≥64 | ≥16 | 4 | ≥16 | 1 | |||||
| 81 | ≥64 | ≥16 | 4 | ≥16 | 1 | |||||
| P12 | 84 | ≥64 | ≥16 | 1 | 2 | 0.125 | None | No (ANI, AMB) | Azole-naïve | Died |
| P13 | 100 | 1 | 0.25 | 0.5 | 1 | 1 | None | No (CASP) | Azole-naïve | Alive |
| P14 | 54 | 4 | ≥ 16 | ≥16 | ≥16 | 1 | No data | No data | Died | |
| Azole non-susceptible isolates + fluconazole tolerant isolates (n = 10) | ||||||||||
| P15 | 94 | 0.5 | 0.032 | 2 | 4 | 8 | None | Yes (FLC changed to MICA) | FLC failure | Died |
| 95 | 1 | 0.032 | 2 | ≥ 16 | 16 | |||||
| 96 | 0.25 | 0.032 | 0.125 | 0.064 | 0.032 | |||||
| 97 | 0.25 | 0.032 | 0.032 | 0.064 | 0.032 | |||||
| P16 | 156 | 0.25 | 0.032 | ≥ 16 | ≥16 | ≥16 | None | Yes (FLC changed to ANI) | FLC failure | Alive |
| 157 | 0.25 | 0.032 | ≥ 16 | ≥ 16 | ≥16 | |||||
| P17 | 158 | 0.25 | 0.032 | ≥ 16 | ≥16 | ≥16 | None | Yes (FLC changed to ANI) | FLC failure | Died |
| P18 | 165 | 0.25 | 0.125 | 0.125 | 1 | 0.032 | None | Yes (FLC changed to ANI) | FLC failure | Alive |
| P19 | 159 | 0.5 | 0.032 | ≥ 16 | ≥16 | 16 | None | None | Azole-naïve | Died |
| P20 | 162 | 0.25 | 1 | 0.125 | 0.064 | 0.125 | None | No (ANI) | Azole-naïve | Alive |
| Fluconazole-tolerant isolates exposed to azoles (n = 23) | ||||||||||
| 23 patients | 23 isolates | 0.25–1 | 0.032 | 0.032–125 | 0.032–0.125 | 0.32 | Yes (n = 2) | Yes (n = 23) | Yes (n = 7)** | Died (n = 7) |
| No (n = 21) | No (n = 16) | Alive (n = 16) | ||||||||
| Fluconazole-tolerant isolates not exposed to azoles (n = 18) | ||||||||||
| 18 patients | 19 isolates | 0.25–0.5 | 0.32–0.064 | 0.032–0.125 | 0.032–0.064 | None | No (n = 14) | NA | Died (n = 9) | |
| No treatment (n = 4) | Alive (n = 9) | |||||||||
* This patient had persisting fever and died while being treated with fluconazole. ** Treatment changed to CASP (n = 1), AMB + ANI (n = 1), ANI (n = 1), VORI (n = 1), AMB (n = 1), or MICA (n = 1); among whom only three died. FLC, fluconazole; VORI, voriconazole; ITRA, itraconazole; POSA, posaconazole; ISA, isavuconazole; AMB, amphotericin B; ANI, anidulafungin; MICA, micafungin; CASP, caspofungin.