Candida krusei should be considered to be resistant to fluconazole. Resistance in C. krusei appears to be mediated by reduced sensitivity of the target enzyme to inhibition by the agent.

There have been reports of cases of superinfection with Candida species other than C. albicans, which are often inherently not susceptible to DIFLUCAN (e.g., Candida krusei). Such cases may require alternative antifungal therapy.

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1
* In a majority of the studies, fluconazole MIC90 values against C. glabrata were above the susceptible breakpoint (≥16 µg/mL). Resistance in Candida glabrata usually includes upregulation of CDR genes resulting in resistance to multiple azoles. For an isolate where the MIC is categorized as intermediate (16 to 32 µg/mL, see Table 1), the highest dose is recommended (see DOSAGE AND ADMINISTRATION ). For resistant isolates, alternative therapy is recommended.

Susceptibility Testing Methods

Cryptococcus neoformans and filamentous fungi
No interpretive criteria have been established for Cryptococcus neoformans and filamentous fungi.

Candida species

Broth Dilution Techniques
Quantitative methods are used to determine antifungal minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of Candida spp. to antifungal agents. MICs should be determined using a standardized procedure. Standardized procedures are based on a dilution method (broth)1 with standardized inoculum concentrations of fluconazole powder. The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion Techniques
Qualitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of Candida spp. to an antifungal agent. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 25 µg of fluconazole to test the susceptibility of yeasts to fluconazole. Disk diffusion interpretive criteria are also provided in Table 1.

Table 1: Susceptibility Interpretive Criteria for Fluconazole   Broth Dilution at 48 hours
(MIC in µg/mL) Disk Diffusion at 24 hours
(Zone Diameters in mm)
Antifungal agent Susceptible
(S) Intermediate
(I)* Resistant
(R) Susceptible
(S) Intermediate
(I)* Resistant
(R)
*
The intermediate category is sometimes called Susceptible-Dose Dependent (SDD) and both categories are equivalent for fluconazole.
†
Isolates of C. krusei are assumed to be intrinsically resistant to fluconazole and their MICs and/or zone diameters should not be interpreted using this scale. 
Fluconazole† ≤ 8.0 16–32 ≥64 ≥19 15–18 ≤14

The susceptible category implies that isolates are inhibited by the usually achievable concentrations of antifungal agent tested when the recommended dosage is used. The intermediate category implies that an infection due to the isolate may be appropriately treated in body sites where the drugs are physiologically concentrated or when a high dosage of drug is used. The resistant category implies that isolates are not inhibited by the usually achievable concentrations of the agent with normal dosage schedules and clinical efficacy of the agent agains