Antifungal drug resistance: does it matter?

The objectives of this review are: to review the modes of action of currently available antifungal drugs; to define drug resistance and discuss the mechanisms by which fungi can develop resistance to antifungal drugs; to consider the epidemiological and host factors that contribute to the outcome of antifungal therapy and whether the available in vitro susceptibility test methods can reliably predict clinical response; and to assess the overall relevance of drug resistance to the outcome of fungal infections. The incidence of antifungal drug resistance among pathogens causing invasive fungal infections appears to be increasing. In the case of Candida spp., this may in part be a consequence of selective pressure brought about by more intensive antifungal use leading to a 'pathogen shift'. Non-albicans Candida spp. are more likely to demonstrate reduced susceptibility to fluconazole compared to C. albicans. Susceptibility breakpoints developed by the National Committee for Clinical Laboratory Standards to test azoles and flucytosine against Candida spp. are helpful in guiding therapy. Antifungal drug resistance in yeasts is of clinical importance. Increasingly reliable methods of in vitro susceptibility testing can help predict clinical response to therapy, but other considerations, including host- and drug-related factors, can also have an important bearing on the ultimate outcome of treatment.