752. Decreased Echinocandin Resistance among Candida glabrata over an Eleven-Year Period at a University Hospital

Abstract

Abstract Background Invasive candidiasis (IC) is associated with significant morbidity and mortality. Echinocandins (ECH; caspofungin (CAS), micafungin (MFG), anidulafungin (AFG)) are first line therapy for IC. ECH resistance has emerged widely, most commonly among Candida glabrata. At some centers, > 10% of C. glabrata are ECH resistant. We reported ECH resistance in 8% of C. glabrata at our hospital from 2008–2014, which prompted stewardship strategies to limit prolonged ECH treatment courses. We evaluated trends of ECH resistance from Jan 2010-Dec 2020 among C. glabrata clinical isolates, and assayed isolates for FKS hot spot (HS) mutations. Methods We mined electronic medical records for ECH MIC data against C. glabrata clinical isolates at UPMC. We defined ECH resistance using Clinical and Laboratory Standards Institute clinical breakpoints. Isolates resistant to any ECH underwent FKS Sanger sequencing. Statistical analysis was performed using Stata. Results Overall CAS, AFG and MFG resistance rates among 516 isolates were 4%, 3%, and 2.5%, respectively. There was no significant difference in resistance rates between blood and non-blood sites (Table 1). There was a significant decrease in MFG resistance over the 12-year period (Fig 1). Time series regression analysis showed a decrease in rate of MFG resistance of 0.73% per year (p=.007). Trends for decreases in AFG and CAS resistance rates were also noted (p=.1 and p=.17). Similar analyses showed annual decreases in MFG MICs (0.019 μg/mL per year; p=.07). The average percentage of AFG resistant isolates was significantly lower in 2017–2020 than in 2012–2016 (p=.04); similar trends were evident for MFG (p=.07) and CAS (p=.08) (Fig 2). Sanger sequencing of FKS1/2 was performed for 27 isolates resistant to ≥1 ECH. Mutations were found in 44% (12/27) of isolates: 5 mutations in HS1 FKS1, 1 in HS2 FKS1, 5 in HS1 FKS2 and 1 in HS2 FKS2. Using both CAS and AFG MICs was most predictive of FKS mutations (Fig. 3). Conclusion ECH resistance among C. glabrata stabilized or decreased over 11-years at our hospital, in keeping with stewardship interventions to reduce prolonged use of ECHs. These results demonstrate that it is feasible to conserve ECH susceptibility. Disclosures Cornelius J. Clancy, MD, receives research funding paid to his institution from Astellas and Merck: Grant/Research Support|serves as an advisory Board member for Astellas, Cidara, and Scynexis, served on the advisory board for Merck, Qpex Biopharma, and Shionogi: Advisor/Consultant|Venatorx and Needham & Associates: Advisor/Consultant Minh-Hong Nguyen, MD, QPX: Grant/Research Support.