International Evaluation of MIC Distributions and Epidemiological Cutoff Value (ECV) Definitions for Fusarium Species Identified by Molecular Methods for the CLSI Broth Microdilution Method

Abstract

rThe CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various Candida spp., Aspergillus spp., and the Mucorales. However, those categorical endpoints have not been established for Fusarium spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53 Fusarium dimerum species complex (SC), 10 F. fujikuroi, 82 F. proliferatum, 20 F. incarnatum-F. equiseti SC, 226 F. oxysporum SC, 608 F. solani SC, and 151 F. verticillioides isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing >97.5% of pooled statistically modeled MIC distributions were as follows: for amphotericin B, 4 g/ml (F. verticillioides) and 8 g/ml (F. oxysporum SC and F. solani SC); for posaconazole, 2 g/ml (F. verticillioides), 8 g/ml (F. oxysporum SC), and 32 g/ml (F. solani SC); for voriconazole, 4 g/ml (F. verticillioides), 16 g/ml (F. oxysporum SC), and 32 g/ml (F. solani SC); and for itraconazole, 32 g/ml (F. oxysporum SC and F. solani SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting nonwild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for Fusarium spp.

Fusarium species causing eumycetoma: Report of two cases and comprehensive review of the literature

“…In our patients, antifungal susceptibility testing showed that F. keratoplasticum had a low MIC of 1 μg/mL against amphotericin B and high MICs above published ECV values for itraconazole (4 μg/mL), voriconazole (4 μg/mL), posaconazole (>16 μg/mL), isavuconazole (8 μg/mL), anidulafungin (>16 μg/mL), micafungin (>16 μg/mL) and fluconazole (>64 μg/mL). F. pseudensiforme had the following MICs; 0.5, >16, 8, 4, 8, >16, >16 and >64 μg/mL for amphotericin B, itraconazole, voriconazole, posaconazole, isavuconazole, anidulafungin, micafungin and fluconazole respectively.…”

Multidrug‐resistant Fusarium in keratitis: a clinico‐mycological study of keratitis infections in Chennai, India

“…This study demonstrated that the Fusarium spp. had high MICs above published epidemiological cut‐off values (ECVs), for itraconazole (16 μg/mL), voriconazole (8 μg/mL) and minimum effective Concentration (MEC) for caspofungin (16 μg/mL). Posaconazole also showed elevated MICs ranging 16‐32 μg/mL (Table ).…”

In vitro synergistic combinations of pentamidine, polymyxin B, tigecycline and tobramycin with antifungal agents against Fusarium spp.

“…For confirmation of Fusarium spp., it has been suggested to sequence for the gene codifying the elongation factor a (O' Donnell et al, 2010). According to recent studies (AlHatmi et al, 2016;Espinel-Ingroff et al, 2016), identification of Fusarium spp. is important because there are differences in relation to the antifungal susceptibility between different species.…”