Fluconazole Resistance In Candida Species

Fluconazole is the most commonly used drug to treat candidiasis. Treatment failure may be due to inherently resistant Candida species or it may be acquired resistance to the drug in Candida species otherwise known to be susceptible to triazoles.
Candida albicans, C. tropicalis, C. parapsilosis are common candida species assumed to be susceptible to fluconazole. Candida krusei is known to be intrinsically resistant to fluconazole but shows very little cross-resistance to higher triazoles like voriconazole. On the other hand, C. glabrata and the newly emerged C. auris exhibit acquired resistance that spans all triazoles. Other less common candida species which can show reduced susceptibility to fluconazole are C.guillermondii,C. rugosa, C. inconspicua, and C.norvegensis.

Triazole susceptibilities to invasive candida species can be determined by recording minimal inhibitory concentration (MICs) using broth microdilution (BMD), e-test strips or zone diameters with triazole discs. The medium used for MIC testing is RPMI broth for BMD and RPMI agar for e-test strips; the cut-off point being the dilution showing more than 50% drop in growth rather than complete inhibition. For disc diffusion, the medium is Mueller-Hinton agar with 2% glucose and 0.5mcg/ml methylene-blue and a 25 mcg disc. The interpretative categories for fluconazole have been revised. Clinical break points of zone diameters and MICs for C. albicans, C. glabrata, C. parapsilosis and C. tropicalis are available with CLSI M60 (2017). For other less common Candida species without clinical breakpoints, epidemiologic cut-off values (as per CLSI M59, or EUCAST ) may be used to determine if the isolate is expressing any acquired resistance or not.

Contributed by
Joveria Farooqi
Assistant Professor and Consultant Microbiologist
Pathology and Laboratory Medicine
Aga Khan University
Karachi
August 2018