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Patients presenting with severe COVID-19 are predisposed to acquire secondary fungal infections such as COVID-19-associated candidemia (CAC), which are associated with poor clinical outcomes despite antifungal treatment. The extreme burden imposed on clinical facilities during the COVID-19 pandemic has provided a permissive environment for the emergence of clonal outbreaks of multiple Candida species, including C. auris and C. parapsilosis . Here we report the largest clonal CAC outbreak to date caused by fluconazole resistant (FLZR) and echinocandin tolerant (ECT) C. parapsilosis . Sixty C. parapsilosis strains were obtained from 57 patients at a tertiary care hospital in Brazil, 90% of them were FLZR and ECT. Although only 35.8% of FLZR isolates contained an ERG11 mutation, all of them contained the TAC1 L518F mutation and significantly overexpressed CDR1 . Introduction of TAC1 L518F into a susceptible background increased the MIC of fluconazole and voriconazole 8-fold and resulted in significant basal overexpression of CDR1 . Additionally, FLZR isolates exclusively harboured E1939G outside of Fks1 hotspot-2, which did not confer echinocandin resistance, but significantly increased ECT. Multilocus microsatellite typing showed that 51/60 (85%) of the FLZR isolates belonged to the same cluster, while the susceptible isolates each represented a distinct lineage. Finally, biofilm production in FLZR isolates was significantly lower than in susceptible counterparts Suggesting that it may not be an outbreak determinant. In summary, we show that TAC1 L518F and FKS1 E1393G confer FLZR and ECT, respectively, in CAC-associated C. parapsilosis . Our study underscores the importance of antifungal stewardship and effective infection control strategies to mitigate clonal C. parapsilosis outbreaks.

Purpose: To investigate the relationship between the mandibular foramen (MF) and the inferior occlusal plane (IOP) of anatomic specimens, in order to guide clinicians in the inferior alveolar nerve block (IANB)., Method: Eighty-two dry mandibles (totally or partially toothed) of Brazilian adults were selected, totalizing 66 left and 66 right antimeres. A flat plate of rigid PVC plastic was placed on the occlusal surfaces of posterior teeth and pressure was then manually applied to simulate the IOP. Following, the perpendicular distance from the IOP to the lowest point of the MF was measured by the use of a digital caliper, adopting negative values inferiorly and positive values superiorly., Results: Regarding the antimeres, the majority of the lowest limits of the MF was below the IOP (right: 86.4%, left: 81.8%) with a mean of -4.2mm (±4.8) in the right and -4.1mm (±4.8) in the left ones, without any statistical significance. Considering both sexes, no statistically significant difference was obtained between them., Conclusion: The IOP seems not to be a good anatomical landmark to localize the MF and, its turn, to guide clinicians during the IANB for Brazilian adults, given the marked topographic variations., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)