In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole, voriconazole and posaconazole (SCH56592)

We investigated the in vitro susceptibilities of 213 cerebrospinal fluid isolates of Cryptococcus neoformans isolated from 192 patients through a 10-year period, 1990-99, against fluconazole, voriconazole and posaconazole (SCH56592) by using the NCCLS (National Committee for Clinical Laboratory Standards) macrodilution method, M27-A. The overall MIC_s50 and MIC_s90 of fluconazole, voriconazole and posaconazole were found to be 2 and 8 μg ml^-1, ≤ 0.125 μg ml^-1 (both), and ≤ 0.015 and 0.06 μg ml^-1, respectively. The MIC ranges, MIC_s50, and MIC_s90 of three triazoles were also determined according to the defined year category (1990-94, 1995, 1996, 1997 and 1998-99). The MIC_s50 and MIC_s90 of each triazole remained almost unchanged and did not exhibit any sign of an upward shift during a decade (1990-99). However, a tendency for development of possible cross-resistance between the three triazoles was observed only in 1996. Meanwhile, the individual relapsing isolates (n:21) from 20 patients exhibited same, higher or, suprisingly, lower MICs, particularly against fluconazole and posaconazole.