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2021 OMIG Abstract
Voriconazole Resistance Varies Across Fusarium Species Complexes in Isolates from the MUTT
Anisha Bhanot1, Marina Brown1, David Giacalone2, Kuppamuthu Dharmalingham3,
Michael E. Zegans2,
and Kevin K. Fuller1
1University of Oklahoma Health Sciences Center, Oklahoma; 2Geisel School of Medicine at Dartmouth,
New Hampshire; 3Aravind Medical Research Foundation, India
Purpose: The key finding from the Mycotic Ulcer Treatment Trial (MUTT) was that voriconazole is inferior to natamycin for treating Fusarium keratitis. Given that Fusarium is a large genus comprised of at least 23 discrete clades/species complexes, we sought to determine (1) which species complexes were represented among the MUTT clinical isolates and (2) if differences in antifungal susceptibility was species complex-dependent.
Methods: 93 Fusarium isolates from the MUTT were identified at the species level by sequencing and BLAST analysis of the internal transcribed spacer (ITS) and translational elongation factor (tef-1) loci. Randomly selected isolates from each of the three represented complexes (8-11/group) were analyzed for their sensitivity to natamycin and voriconazole in a microtiter dilution assay. Microconidia were inoculated into RPMI 1640 media (supplemented with 2% glucose) and incubated for 48 h at 35oC. Mean MICs for each species complex were compared using an ANOVA and Student’s t-test.
Results: ITS and tef-1 sequence analysis revealed that 80% of the tested isolates belonged to the Fusarium solani species complex (FSSC), 12% to the Fusarium dimerum species complex (FDSC) and 8% to the Fusarium fujikuroi species complex (FFSC). Whereas the mean MIC to voriconazole for FDSC (8.63 µg/mL) and FFSC (12.46 µg/mL) were statistically indistinguishable from each other, both were statistically more sensitive compared to the FSSC (39.11 µg/mL). The mean MIC to natamycin was equivalent between the FFSC (10 µg/mL) and FFSC (13.3 µg/mL), but both were statistically resistant compared to the FDSC (5.8 µg/mL).
Conclusions: FSSC isolates are more resistant to voriconazole, but not natamycin, compared than the other Fusarium clades present in the MUTT. In the case of the FDSC and FFSC, the MIC values for voriconazole and natamycin were comparable. As the FSSC is by far the most prevalent Fusarium clade in the MUTT (80%), these data may explain why voriconazole was demonstrably inferior to natamycin during the trial. Taken together, these results underscore the importance of species level identification of clinical specimens for informing treatment of fungal keratitis.
Disclosure: N
Support: NIH/NEI grant R21EYE28677-01 (MEZ, KKF); RPB Career Development Award (KKF)
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