The prevalence of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E) has increased by over 50% in the US over a 5-year period - with upwards of 30% mortality associated with ESBL-E bloodstream infections (BSI). Our preliminary data across Enterobacterales species indicate that 3 ESBL gene families comprise ~99% of ESBLs (i.e., blaCTX-M [60%], blaSHV-variants [25%], and blaTEM-variants [15%]); however, little progress has been made to characterize the prevalence of non-CTX-M gene families across Enterobacterales species and it is unknown if piperacillin-tazobactam may be an effective carbapenem-sparing treatment option for SHV and TEM ESBL-E infections. We would like to investigate if a mechanistic-based treatment approach (i.e., optimal antibiotic treatment selection is dependent on the ESBL gene identified) will improve the outcomes of patients by (1) characterizing the epidemiology of ESBL genes in a multicenter cohort of 2,000 consecutive clinical Enterobacterales BSI isolates and (2) determining if meropenem is the preferred treatment for ESBL-producing Enterobacterales BSI regardless of the ESBL gene family present.