Lack of correlation between fluconazole and voriconazole MIC values and disk inhibition zones diameters in clinical Cryptococcus neoformans strains.

THEILL L; FROLA C; LEONARDELLI, F.; GUELFAND, L; MACEDO, D.; CABEZA, M.S.; DUDIUK, CATIANA; GARCIA, G.; GAMARRA, S.

Buenos Aires

Congreso; XVIII Congreso Argentino de la Sociedad Argentina de Infectología/XVIII Congress of the international society of Infectious Diseases. 2018.; 2018

SADI

The treatment of choice for Cryptococcus neoformans infections is amphotericin B combined with flucytosine. In Argentina, the fluorinated pytimidine analog is not available and amphotericin B is combined with fluconazole. Considering the high frequency of treatment failures, antifungal susceptibility testing (AST) is needed. There are two CLSI reference methods available to perform yeast AST: documents M27A3/S4 (in broth) and M44A2 (disk diffusion). The first method is difficult to use in hospital settings and is suggested to be used for Candida spp. and Cryptococcus spp. Conversely, disk diffusion method is proposed only for Candida spp.. Our aim was to analyze the correlation of M27A3/S4 and M44A2 documents for the evaluation of in vitro activity of fluconazole and voriconazole against C. neoformans clinical isolates. The reference CLSI method M27A3/S4 was used to determine fluconazole and voriconazole minimal inhibitory concentrations. OxoidTM disks and Mueller Hinton 2% glucose (M44A2) was tested as a possible subrogate against 88 C. neoformans strains. The inhibition zones were read at 48 and 72 hours.MIC geometric means were 4.13 µg/ml and 0.06 µg/ml for fluconazole and voriconazole, respectively. 31.8% of the strains showed MICs above the established epidemiological cut off to consider an isolate as fluconazol non-wild type and none were considered non-wild type for voriconazole. A wide variability in inhibition diameters was observed when 48 and 72 hours readings were used. For fluconazole, the diameters ranged from 12 to 43 cm at 48 hours and from 1 to 43 cm at 72 hours. The 28 fluconazole non-wild type strains showed a diameter range of 12-36 cm and 1-27 cm when read at 48 and 72 hs, respectively. Turning to wild type population, the diameter ranges for fluconazole were 12-43 and 10-43 cm. For voriconazole the diameters ranged from 23 to 53 and from 13 to 50 cm.When comparing the fluconazole disk inhibition zones obtained for wild-type and non-wild-type populations data show that there is an important diameter overlapping discarding the possibility of using M44A2 document as a subrogate AST method for Cryptococcus spp. and fluconazole.