1254. Molecular Epidemiology of Escherichia coli Causing Urinary Tract Infections in United States and in vitro Activity of Tebipenem, Including Against Strain Lineage and Resistant subsets (2018-2020)

Abstract Background Tebipenem (TBP) is an oral carbapenem in clinical development for treating complicated urinary tract infections (UTIs), including pyelonephritis. This study investigates the epidemiology of E. coli (EC) causing UTI in U.S. patients and the activity of TBP and comparators against various subsets. Methods A total of 2,395 EC recovered from urine samples during the 2018-2020 STEWARD Surveillance Program were included. Isolates were collected from medical centers in all 9 US Census Regions and centrally tested by reference broth microdilution method. MIC interpretation was based on CLSI criteria. Isolates that met MIC criteria were subjected to genome sequencing, followed by screening of extended-spectrum β-lactamase (ESBL) genes and epidemiology typing (MLST). Results A total of 16.1%, 15.4% and 14.6% of EC met the ESBL screening criteria in 2018, 2019 and 2020, respectively. 269/360 (74.7%) carried blaCTX-M and 2/360 (0.6%) had blaSHV-12. blaCMY (33/360; 9.2%) was the most common cephalosporinase, followed by blaDHA (7/360; 1.9%). A CRE phenotype was noted in 1 isolate from New York, which carried blaKPC-2. Acquired genes were not detected in 56 strains. 50 ST types were noted in isolates that met the ESBL criteria screening, with the majority of isolates being ST131 (56.2%). 21 (6.7%) and 19 (6.0%) isolates belonged to ST38 and ST1193, respectively, followed by STs represented by 8 or less isolates. Among ST131, 56.5% carried blaCTX-M from group 1 and 35.6% had genes associated with group 9. Overall, TBP showed consistent MIC50 values throughout the subsets. ERT had activity (≥97.0% susceptible) against the various subsets; however, lower susceptibility rates (85.7-90.6%) were noted against isolates carrying plasmid AmpC. Other agents (ceftriaxone and cefazolin) had activity only against non-ESBL producers. Conclusion bla CTX-M comprised the majority of acquired genes detected among ESBL strains, which belonged mostly to ST131, emphasizing the expansion of this clone. TBP showed consistent activity against all subsets, regardless of resistance genotype or lineage. These data support the clinical development of TBP as a convenient oral treatment option for UTI caused by EC. Disclosures Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Timothy B. Doyle, AbbVie (formerly Allergan) (Research Grant or Support)Bravos Biosciences (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Ian A. Critchley, Ph.D., Spero Therapeutics (Employee, Shareholder) Nicole Cotroneo, Spero Therapeutics (Employee, Shareholder) Jennifer M. Streit, BS, GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) 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. (Individual(s) Involved: Self): Research Grant or Support; BioVersys Ag (Individual(s) Involved: Self): Research Grant or Support; Bugworks (Individual(s) Involved: Self): Research Grant or Support; Cidara (Individual(s) Involved: Self): Research Grant or Support; Cipla (Individual(s) Involved: Self): Research Grant or Support; Contrafect (Individual(s) Involved: Self): Research Grant or Support; Cormedix (Individual(s) Involved: Self): Research Grant or Support; Crestone, Inc. (Individual(s) Involved: Self): Research Grant or Support; Curza (Individual(s) Involved: Self): Research Grant or Support; CXC7 (Individual(s) Involved: Self): Research Grant or Support; Entasis (Individual(s) Involved: Self): Research Grant or Support; Fedora Pharmaceutical (Individual(s) Involved: Self): Research Grant or Support; Fimbrion Therapeutics (Individual(s) Involved: Self): Research Grant or Support; Fox Chase (Individual(s) Involved: Self): Research Grant or Support; GlaxoSmithKline (Individual(s) Involved: Self): Research Grant or Support; Guardian Therapeutics (Individual(s) Involved: Self): Research Grant or Support; Hardy Diagnostics (Individual(s) Involved: Self): Research Grant or Support; IHMA (Individual(s) Involved: Self): Research Grant or Support; Janssen Research & Development (Individual(s) Involved: Self): Research Grant or Support; Johnson & Johnson (Individual(s) Involved: Self): Research Grant or Support; Kaleido Biosceinces (Individual(s) Involved: Self): Research Grant or Support; KBP Biosciences (Individual(s) Involved: Self): Research Grant or Support; Luminex (Individual(s) Involved: Self): Research Grant or Support; Matrivax (Individual(s) Involved: Self): Research Grant or Support; Mayo Clinic (Individual(s) Involved: Self): Research Grant or Support; Medpace (Individual(s) Involved: Self): Research Grant or Support; Meiji Seika Pharma Co., Ltd. (Individual(s) Involved: Self): Research Grant or Support; Melinta (Individual(s) Involved: Self): Research Grant or Support; Menarini (Individual(s) Involved: Self): Research Grant or Support; Merck (Individual(s) Involved: Self): Research Grant or Support; Meridian Bioscience Inc. (Individual(s) Involved: Self): Research Grant or Support; Micromyx (Individual(s) Involved: Self): Research Grant or Support; MicuRx (Individual(s) Involved: Self): Research Grant or Support; N8 Medical (Individual(s) Involved: Self): Research Grant or Support; Nabriva (Individual(s) Involved: Self): Research Grant or Support; National Institutes of Health (Individual(s) Involved: Self): Research Grant or Support; National University of Singapore (Individual(s) Involved: Self): Research Grant or Support; North Bristol NHS Trust (Individual(s) Involved: Self): Research Grant or Support; Novome Biotechnologies (Individual(s) Involved: Self): Research Grant or Support; Paratek (Individual(s) Involved: Self): Research Grant or Support; Pfizer (Individual(s) Involved: Self): Research Grant or Support; Prokaryotics Inc. (Individual(s) Involved: Self): Research Grant or Support; QPEX Biopharma (Individual(s) Involved: Self): Research Grant or Support; Rhode Island Hospital (Individual(s) Involved: Self): Research Grant or Support; RIHML (Individual(s) Involved: Self): Research Grant or Support; Roche (Individual(s) Involved: Self): Research Grant or Support; Roivant (Individual(s) Involved: Self): Research Grant or Support; Salvat (Individual(s) Involved: Self): Research Grant or Support; Scynexis (Individual(s) Involved: Self): Research Grant or Support; SeLux Diagnostics (Individual(s) Involved: Self): Research Grant or Support; Shionogi (Individual(s) Involved: Self): Research Grant or Support; Specific Diagnostics (Individual(s) Involved: Self): Research Grant or Support; Spero (Individual(s) Involved: Self): Research Grant or Support; SuperTrans Medical LT (Individual(s) Involved: Self): Research Grant or Support; T2 Biosystems (Individual(s) Involved: Self): Research Grant or Support; The University of Queensland (Individual(s) Involved: Self): Research Grant or Support; Thermo Fisher Scientific (Individual(s) Involved: Self): Research Grant or Support; Tufts Medical Center (Individual(s) Involved: Self): Research Grant or Support; Universite de Sherbrooke (Individual(s) Involved: Self): Research Grant or Support; University of Iowa (Individual(s) Involved: Self): Research Grant or Support; University of Iowa Hospitals and Clinics (Individual(s) Involved: Self): Research Grant or Support; University of Wisconsin (Individual(s) Involved: Self): Research Grant or Support; UNT System College of Pharmacy (Individual(s) Involved: Self): Research Grant or Support; URMC (Individual(s) Involved: Self): Research Grant or Support; UT Southwestern (Individual(s) Involved: Self): Research Grant or Support; VenatoRx (Individual(s) Involved: Self): Research Grant or Support; Viosera Therapeutics (Individual(s) Involved: Self): Research Grant or Support; Wayne State University (Individual(s) Involved: Self): Research Grant or Support

treat organisms, including cephalosporin-and carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. The activity of the investigational combination cefepime-taniborbactam (FTB) and comparator agents was evaluated against clinical isolates of Enterobacterales from a 2018-2020 global surveillance study.
Methods. MICs of cefepime with taniborbactam fixed at 4 µg/mL and comparators were determined following CLSI M07-A11 guidelines against 10,543 Enterobacterales. Isolates were from community and hospital infections collected from 259 sites in 56 countries in 2018-2020. Resistant phenotypes were based on 2021 CLSI breakpoints. A set of 827 isolates with meropenem MIC ≥4 µg/mL (n=421) or with cefepime and/or ceftazidime MIC ≥2 µg/mL (n=406) was evaluated for the presence of MBLs, KPC, ESBLs, and OXA-48 group genes via PCR and sequencing. Forty-eight isolates with FTB MIC values of 16 µg/mL or greater were interrogated by WGS.
Results Table   Conclusion. Taniborbactam significantly restored the in vitro activity of cefepime against Enterobacterales, including isolates nonsusceptible to recently-approved BL/ BLI combinations and expressing serine and metallo-β-lactamases. This support the continued development of FTB as a potential new treatment option for challenging infections due to resistant Gram-negative pathogens.
Disclosures Methods. A total of 2,395 EC recovered from urine samples during the 2018-2020 STEWARD Surveillance Program were included. Isolates were collected from medical centers in all 9 US Census Regions and centrally tested by reference broth microdilution method. MIC interpretation was based on CLSI criteria. Isolates that met MIC criteria were subjected to genome sequencing, followed by screening of extended-spectrum β-lactamase (ESBL) genes and epidemiology typing (MLST).
Conclusion. bla CTX-M comprised the majority of acquired genes detected among ESBL strains, which belonged mostly to ST131, emphasizing the expansion of this clone. TBP showed consistent activity against all subsets, regardless of resistance genotype or lineage. These data support the clinical development of TBP as a convenient oral treatment option for UTI caused by EC.