Trends of Echinocandin Resistance in Candida glabrata over an Eleven-Year Period at a University HospitalRaabe, Nathan (2022) Trends of Echinocandin Resistance in Candida glabrata over an Eleven-Year Period at a University Hospital. Master Essay, University of Pittsburgh.
AbstractBackground/Objective: Invasive Candida infections (invasive candidiasis, IC) are responsible for significant morbidity and mortality, especially in immunocompromised populations. Echinocandins (ECH; caspofungin, micafungin, anidulafungin) are the gold standard treatment for IC. Unfortunately, their expanding use promoted the emergence of resistance among Candida species, especially Candida glabrata. The molecular mechanisms underlying resistance include point mutations within hot spots (HS) of FKS genes which encode subunits of fungal glucan synthase. The overall goals of this project were to evaluate the trend of ECH resistance over an 11-year period among C. glabrata clinical isolates and to associate caspofungin, anidulafungin and micafungin minimum inhibitory concentrations (MICs) with mutations within the HS of FKS genes. Methods: We retrospectively collected ECH MIC data that were performed for C. glabrata clinical isolates over 11 years (2010-2020) at UPMC Presbyterian campus. We defined ECH resistance using Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints (CBPs). Isolates resistant to any ECH underwent FKS gene Sanger sequencing. Statistical analysis was performed using Stata. Results: Based on CBPs, 4%, 3%, and 2.5% of isolates were resistant to CAS, AFG and MFG, respectively. The average resistance rate observed between 2012-2016 was higher than that of 2017-2020 for each ECH (CAS 5.5% vs 2.1%, AFG and MFG 4.6% vs 0.85%). There was a significant difference between the proportion of isolates resistant to ≥1 ECH in 2012-2016 compared to 2017-2020 (7.5% vs 2.5%, p=0.021). From 2012-2020, there was a significant decline in the rate of MFG resistance of 0.73% per year (p=0.007), and trends for CAS and AFG followed a similar pattern as MFG (p=0.099, p=0.166). Using both CAS and AFG MICs was most predictive of FKS mutations. No significant difference in resistance rates existed between blood and non-blood collection sites. Conclusion: Over the 11-year period, trends of ECH resistance have stabilized or decreased, reflecting antibiotic stewardship efforts to reduce prolonged use of ECHs at our center. These results provide evidence that conserving ECH susceptibility is possible. Further efforts to examine the factors that drive local antifungal resistance rates are warranted both nationally and internationally to improve public health outcomes for invasive candidiasis patients. Share
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