Original Research
Tuesday, November 14, 2023
08:30 AM–10:00 AM
Abstract
Introduction:
As our understanding of the reciprocal interaction between pharmaceuticals and the gut microbiome deepens, the potential consequences for antimicrobial resistance (AMR) in intestinal bacteria have increasingly become a point of interest. Quetiapine, a commonly prescribed second-generation antipsychotic (SGA) drug, has been implicated in this context. Our prior research has shown that quetiapine contributes to AMR
in vitro; however, the impact of this interaction are unclear. In this study, we aimed to understand the impact of quetiapine on the gut resistome of mice.
Research Question or Hypothesis: We hypothesize that long-term exposure of gut bacteria to quetiapine will select for genetic adaptations that are shared with AMR mechanisms.
Study Design: Longitudinal, parallel-controlled, repeated measures animal intervention study with quetiapine
Methods: Male and female adult mice were exposed to quetiapine (10 mg/kg/day) via drinking water over a 12-week period. The fecal resistome was assessed longitudinally and compared to a parallel control group that received regular drinking water. We utilized a hybrid capture approach to survey longitudinal dynamics of AMR genes and gene variants. We evaluated the minimal inhibitory concentrations (MICs) of Escherichia coli isolates cultured from mouse stool to assess changes in antibiotic susceptibility.
Results: We found that quetiapine exposure increased the relative abundance of AMR gene families related to antibiotic efflux (Qvalue = 0.03) , the phosphoethanolamine transferases (Qvalue = 0.05), and undecaprenyl pyrophosphate-related proteins (Qvalue = 0.05) in the fecal resistome. Consistent with these findings, E. coli cultured from quetiapine-exposed mice displayed a significant decrease in colistin sensitivity when compared to E. coli cultured from control mice (Wilcoxon = 0.02).
Conclusion: This study provides the first evidence that quetiapine could contribute to AMR development in complex microbial communities in vivo. These findings underline the importance of further research into the effects of psychiatric medication on the gut resistome to inform more effective clinical practice and antimicrobial stewardship.
Presenting Author
Stephanie Flowers Pharm.D., Ph.D.University of Illinois at Chicago
Authors
Yasuhiro Kyono PhD
University of Illinois at Chicago
Jonathan Magboo HS
University of Illinois at Chicago
Elizabeth Daley BS
University of Illinois at Chicago