228. Epidemiology and Susceptibility Profiles of ST131-O25b Escherichia coli Detected Among Cephalosporin and/or Carbapenem-Resistant Isolates Collected in United States Hospitals

Abstract Background ST131 Escherichia coli possess virulence genes, adaptability for human colonization and are often associated to resistance genes. We evaluated the prevalence, O-antigen and susceptibility profiles of ST131 among β-lactam resistant E. coli isolates collected in US hospitals. Methods A total of 6,768 E. coli isolates collected during 2017 and 2018 were susceptibility tested using reference broth microdilution method. Among these, 1,154 displayed MIC values >1 mg/L against 2 of the following: ceftazidime, ceftriaxone, cefepime or aztreonam or resistance to imipenem or meropenem (CLSI breakpoints) and were submitted to whole genome sequencing (WGS) and data analysis (MLST and O antigen). The genes wzx, wzy, wzm, and wzt were used to identify the O-antigen. Reference guided assembly for gene cluster O-AGC was used to differentiate O25a and O25b. Results Among the WGS E. coli isolates, 627 (54.3%) belonged to ST131 or were single loci variants (SLVs; 1 allele difference). A total of 586 (93.5% of ST131 and 50.8% of sequenced isolates) belonged to the O25b serotype. The remaining 41 isolates belonged to serotypes O16 (40 isolates) or O153var1 (1). ST131 isolates and O25b isolates were considerably more resistant to fluoroquinolones (92.0%-93.3% and 94.7%-95.5%, respectively) when compared to the overall WGS isolate collection (75.6%-77.0%). ST131-O25b isolates were more resistant to 12 /16 antimicrobial agents analyzed, including all β-lactam agents (0.9%-12.7% more resistant), fluoroquinolones (34.5-41.0%), and aminoglycosides (1.2-37.3%). ST131 (49.0%) and ST131-O25b (51.5%) isolates had higher multi-drug resistant (MDR) rates compared to all E. coli isolates (7.3%), WGS isolates (41.4%), and isolates that did not carry these traits (32.4% for non-ST131 and 12.2% for non-O25b). Conclusion ST131 and ST131-O25b E. coli isolates were common among β-lactam resistant E. coli from US hospitals. These isolates were significantly more resistant than their counterparts, despite the elevated resistance rates of the overall WGS collection. ST131-O25b E. coli isolates have the potential to present a challenge for antimicrobial treatment. Specific therapies that are effective against these isolates should be investigated. Disclosures Mariana Castanheira, PhD, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)Cidara Therapeutics, Inc. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Qpex Biopharma (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Mariana Castanheira, PhD, Affinity Biosensors (Individual(s) Involved: Self): Research Grant or Support; Allergan (Individual(s) Involved: Self): Research Grant or Support; Amicrobe, Inc (Individual(s) Involved: Self): Research Grant or Support; Amplyx Pharma (Individual(s) Involved: Self): Research Grant or Support; Artugen Therapeutics USA, Inc. (Individual(s) Involved: Self): Research Grant or Support; Astellas (Individual(s) Involved: Self): Research Grant or Support; Basilea (Individual(s) Involved: Self): Research Grant or Support; Beth Israel Deaconess Medical Center (Individual(s) Involved: Self): Research Grant or Support; BIDMC (Individual(s) Involved: Self): Research Grant or Support; bioMerieux Inc. 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Background. 'One Health' recognizes the interconnectivity of humans with their production and companion animals, and the environment. Emergence and transmission of antimicrobial resistance (AMR) within and between these compartments is a recognized global threat that requires further understanding to design interventions protecting both human and animal health. In this study we identified resistance gene targets and clonotypes of Escherichia coli recovered from human, canine and bovine hosts and applied non-linear dimensionality reduction and visualization techniques to identify genetic relationships that may otherwise be unobservable within the data.
Methods. Non-duplicative E. coli isolates (N=3398; see Figure captions) were collected from humans, canines, bovines from the Midwest USA. We identified beta-lactamase gene targets for third-generation cephem multidrug resistant isolates and performed clonotype analysis on each. Uniform Manifold Approximation (UMAP) was used to create a two-dimensional "map" of the high dimensional space of the genetic results to identify similarities between both infecting and colonizing isolates, and between susceptible and resistant isolates in humans and animals in the study region (see Figure captions).
Results. The resulting "map" highlights similarities in: 1) genetic patterns of AMR among animals and humans, and 2) links between isolates that are infecting and colonizing in humans and canines (Figures 1-2). Our results suggest that there is strong genetic overlap linking human and animal patterns of AMR. UMAP also identified genetic segments that are unique to humans, distinct outliers, and suggest limited exchange among the neighboring counties ( Figure 3). Each panel of the figure shows the same UMAP space with the labeled species in color and the other points in grey as a reference. The UMAP space is a non-linear two-dimensional representation of the genetic information contained in the clonotype analysis. UMAP is a dimensionality reduction technique similar to principal component analysis (PCA), except that it uses a non-linear combination of the underlying dimensions, which highlights the local structure and grouping of the cases. For more details see: Diaz-Papkovich, A., Anderson-Trocmé, L., & Gravel, S. (2021). A review of UMAP in population genetics. Journal of Human Genetics, 66(1), 85-91. Infection isolates: no bovine isolates tested, canine n=190, human n=115. Surveillance isolates: bovine n=175, canine n=747, human n=2171. This figure plots the same cases on the same UMAP space as Figure 1. The only difference is the color that distinguishes between resistant and susceptible cases. Resistant isolates: bovine n=91, canine n=300; human n=238. Susceptible isolates: bovine n=84. canine=637, human n=2048. The dark bars show the proportion of cases falling into each cluster for each county. The light bars provide a reference point for interpreting the dark bars by showing the proportion of cases falling into each cluster across all four counties. When the dark bars exceed the light bars it indicates that the proportion of cases in that cluster exceeds that of the neighboring counties, such as Cluster 2 for Taylor county and Cluster 3 for Marathon county. All counties shown include a population of at least 20,000. These stipulations are in compliance with federal (HIPAA) guidelines.
Conclusion. The results support that UMAP is a valuable tool for visualizing genetic AMR links across species. Human-animal transmission is likely for disparate and common clonotypes.
Disclosures. All Authors: No reported disclosures