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We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (&lt;/=200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 mug/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 mug/ml and 219.36 [P = 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC &lt;/= 8 mug/ml), susceptible-dose dependent (S-DD) (MIC = 16 or 32 mug/ml), and resistant (MIC &gt;/= 64 mug/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio &gt;50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio &lt;/=50 (P = 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.

Fluconazole MIC and the Fluconazole Dose/MIC Ratio Correlate with Therapeutic Response among Patients with Candidemia