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 CLSI guidelines for antifungal susceptibility testing of yeasts. Results for calendar years 2005-2010 are shown below.

 

 

The 2009-2010 results show that 17% of C. glabrata invasive isolates would not be expected to respond to fluconazole therapy regardless of dosage, and that 31% 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 2006-2007 data show a marked increase in the number of fluconazole-susceptible isolates in comparison to 2005, but that over the last two years the frequency of susceptible organisms is on the decline.

Data from 2007 show that non-C. glabrata blood isolates are 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. Of the 17 non-C. glabrata isolates tested in 2009-April 2010, all but one C. famata isolate (mic 8) had fluconazole MICs less than 4 mg/L.

 

There is a reasonable correlation between MIC and clinical outcome, one reasonable predictor being the AUC/MIC ratio. AUC/MIC >10 to 20 seem predictive of better outcome than AUC/MIC<10-20. The AUC for a 400 mg dose is around 300, and around 600 for a 800 mg dose in patients with normal renal function. This study suggests that the outcome of patients with "R" isolates would be unlikely to respond to dosages up to 800 mg/d, but that isolates with lower MICs would be likely to respond to dosages of 800 mg/d or lower.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.

updated 5/13/10 P. Edelstein