MULTICENTER EVALUATION OF THE ETEST METHOD FOR ANTIFUNGAL DRUG SUSCEPTIBILITY TESTING OF CANDIDA SPP. AND CRYPTOCOCCUS-NEOFORMANS

Ten laboratories tested 18 isolates of Candida spp. and two of Cryptoc occus neoformans against amphotericin B, flucytosine, fluconazole and itraconazole on two occasions by the Etest method. Two individuals rea d each set of results. Of the 18 isolates of Candida spp., five were d uplicated, but the participants were not told this. In 40 of the 60 dr ug-organism combinations studied, at least 80% of the Etest MICs fell within a five-concentration range corresponding to the modal MIC +/- 1 log(2) dilution. In five combinations, >50% of the Etest MICs fell ou tside this five-concentration range. In 17 (85%) of the 20 drug-organi sm combinations tested in duplicate, at least 80% of the paired Etest results fell within two concentrations of each other (corresponding to one log, dilution). Overall, 88.5% of the paired Etest results for am photericin B agreed to within two concentrations, as did 94% of result s for flucytosine, 92% for fluconazole and 79% for itraconazole. The b roth microdilution MICs of the four antifungal agents for the 15 isola tes were measured on five occasions in the Mycology Reference Laborato ry, Bristol. In each case, the results fell within a three log(2) conc entration range. In 24 (40%) of the 60 drug-organism combinations test ed, at least 80% of the Etest results fell within the broth microdilut ion test MIC range, but 27 (45%) showed <50% exact agreement. In 33 (7 3%) of 45 drug-organism combinations involving flucytosine, fluconazol e or itraconazole, at least 80% of the Etest results fell within the s ame class (susceptible, resistant, or susceptible dependent upon dose) as the broth microdilution results. With fluconazole, the Etest metho d misclassified three susceptible isolates of Candida spp. as resistan t in 1.5-15% of tests. With itraconazole, the Etest misclassified seve n susceptible isolates of Candida spp. as resistant in 5-62.5% of test s. The Etest also misclassified both C. neoformans isolates as resista nt to flucytosine, fluconazole and itraconazole in 7.5-65% of tests. O ur results suggest that the Etest is suitable for routine use with Can dida spp. and amphotericin B or flucytosine. It is less reliable for t he azoles, and isolates that appear to demonstrate acquired resistance should be retested with well-established reference methods.