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Introduction: Empiric antimicrobial selection in ECMO patients is complicated by evolving resistance patterns and host-related factors. This study aimed to characterize five-year susceptibility trends among Gram-negative rods (GNRs) isolated from ECMO patients. Methods: We reviewed cultures from 81 ECMO patients treated between 2019 and 2023, focusing on GNRs. All isolates collected during ECMO support were included to reflect dynamic resistance changes. Percent susceptibilities were calculated per organism-antibiotic pair, and temporal trends were evaluated using linear regression. Organism-antibiotic combinations with intrinsic resistance or inconsistent testing were excluded. We used AI-assisted tools for statistical coding and editorial refinement. Results: Ertapenem maintained >95% susceptibility throughout all years. Meropenem showed a transient drop in 2022 (62.9%) but recovered to 100% by 2023. Cefepime susceptibility was variable: 88.2% for Serratia marcescens, 75.7% for Klebsiella pneumoniae, 71.4% for Pseudomonas aeruginosa, 95.2% for Klebsiella aerogenes, and 100% for both Enterobacter cloacae and Escherichia coli. In contrast, cefepime susceptibility among Acinetobacter baumannii was only 12.5%. Ampicillin-sulbactam susceptibility improved steadily over time (+11.6% per year; R2 = 0.67; p = 0.088), potentially reflecting reduced usage. Ciprofloxacin susceptibility peaked in 2020–2021 before declining in 2023. Due to inconsistent data, piperacillin-tazobactam was excluded from trend analysis. Conclusions: Antimicrobial susceptibility patterns among GNRs in ECMO patients have fluctuated over the past five years. Carbapenems remain reliable, while recovery of susceptibility to narrower-spectrum agents such as ampicillin-sulbactam and cefepime suggests a potential role for empiric antibiotic cycling. ECMO-specific antibiograms provide critical guidance for treatment and support the role of stewardship in curbing MDRO development in this high-risk population.