Fluconazole resistance of invasive isolates of Candida glabrata and other Candida spp.

The HUP Clinical Microbiology Laboratory determines the fluconazole MIC for blood isolates of C. glabrata routinely, using a FDA-cleared commercial microtiter panel. Other invasive isolates are tested on request. The methodology adheres to NCCLS guidelines for antifungal susceptibility testing of yeasts. Results for calendar years 2003-2007 are shown below.

The 2007 results show that 8% of C. glabrata invasive isolates would not be expected to respond to fluconazole therapy regardless of dosage, and that 10% of the isolates would require dosage higher than the usually recommended dosage of 200 mg/day for those with normal renal function ("SDD", or "sensitive, dose dependent"). Note that the 2007 data show a marked increase in the number of fluconazole-susceptible isolates in comparison to prior years.

The non-C. glabrata blood isolates are in contrast quite susceptible to fluconazole, with much lower fluconazole MICs than for C. glabrata. C. albicans is the most susceptible (and most common blood yeast isolate), with C. parapsilosis being intermediate in susceptibility and frequency between C. albicans and C. glabrata. Note that only one C. albicans isolate (2.2% of all C. albicans isolates) had an elevated fluconazole MIC.

There is a reasonable correlation between MIC and clinical outcome, with infections caused by isolates with MICs>8 having a significantly worse outcome (~20% mortality vs. ~50% mortality). Data from one retrospective study shows that there is an apparently good predictor of outcome with the ratio of daily dose (expressed as mg/kg/day) to MIC, with values >15 associated with a much better outcome than those with values <15. With a modal MIC of 8 for our isolates, this would equate to a modal ratio of 1.5 for ~800 mg/d dose. This study, if confirmed, suggests that the outcome of patients with "SDD" isolates might be better when they are treated with an alternative drug. Note that these relationships does not hold for urine isolates, which may respond to therapy regardless of MIC, because of high drug urine concentrations (~64-128 ug/mL after 400 mg dose), assuming normal renal function.