Azole resistance of invasive isolates of Candida glabrata and other Candida spp. Jan-Dec 2014

The HUP Clinical Microbiology Laboratory determines the fluconazole MIC for blood and invasive isolates of Candida spp., using a FDA-cleared commercial microtiter panel. Other invasive isolates are tested on request. The methodology adheres to CLSI guidelines (M27-S4, Dec 2012) for antifungal susceptibility testing of yeasts. Susceptibility categories include "susceptible" (S), "susceptible dose dependent" (SDD) and "resistant" (R). SDD means that the MIC is high, but that increased dosing of the agent has the potential to inhibit the yeast in vivo; CLSI defines this as "Susceptibility is dependent on achieving the maximal possible blood level (of the drug). For fluconazole, doses higher than the standard dosing (6 mg/kg/d) amount may be required in adults with normal renal function and body habitus". The MIC breakpoints are different between Candida species, based on the MIC population distribution for wild type organisms.

There are no fluconazole MIC breakpoints for C. krusei, which is considered intrinsically resistant to the drug. CLSI has been unable to define a voriconazole breakpoint for C. glabrata. It is unlikely that voriconazole will be effective for the treatment of invasive infection caused by C. glabrata that is fluconazole resistant. Because C. glabrata infection can be difficult to treat with lower doses of fluconazole, there is no susceptible category for that drug for C. glabrata, only susceptible dose dependent, regardless of fluconazole MIC.

For Candida spp. other than those with defined CLSI breakpoints, only azole MICs without interpretation are reported.

 


Fluconazole

CLSI Breakpoints for Azoles

Antifungal Agent Species MIC (mg/L)
S SDD R
Fluconazole C. albicans ≤2 4 ≥8
C. glabrata - ≤32 ≥64
C. krusei intrinsic resistance
C. parapsilosis ≤2   ≥8
C. tropicalis ≤2   ≥8
Voriconazole C. albicans ≤0.12   ≥1
C. glabrata no defined breakpoints
C. krusei ≤0.5   ≥2
C. parapsilosis ≤0.12   ≥1
C. tropicalis ≤0.12   ≥1

Susceptibility Summary Data

Blood Isolates
Antifungal Agent Species N %S %SDD %R
Fluconazole C. albicans 32 97 0 3
  C. glabrata 21 0 100 0
  C. parapsilosis 16 94 6 0
  C. tropicalis 13 100 0 0
Voriconazole C. albicans 32 97 3 0
  C. krusei 3 3/3 0 0
  C. parapsilosis 16 100 0 0
  C. tropicalis 13 100 0 0

 

Non-Blood Isolates
Antifungal Agent Species N %S %SDD %R
Fluconazole C. albicans 30 87 3 10
  C. glabrata 13 0 100 0
  C. parapsilosis 6 6/6 0 0
  C. tropicalis 4 4/4 0 0
Voriconazole C. albicans 30 90 3 7
  C. parapsilosis 6 6/6 0 0
  C. tropicalis 4 4/4 0 0

 

 

 

Where are the caspofungin data?

Caspofungin susceptibility testing is best inferred from another echinocandin susceptibility test, such as micafungin. This is because of technical issues that prevent accurate determination of caspofungin activity. On request, our lab will send an isolate to a reference laboratory for micafungin susceptibility testing, which is considered an excellent surrogate marker for caspofungin activity.

 

12/8/2014 P. Edelstein

Archived data on Candida susceptibility from 2005-2010

Archived data from 2011-2013