Abstract
<jats:p>Carbapenem-resistant Escherichia coli (CREc) recovered sequentially from one patient typically retain the same carbapenemase, with escalating resistance usually attributed to porin loss combined with pre-existing β-lactamase expression. We used whole-genome sequencing to characterize a clonal pair of CREc isolates, CAEC145 and CAEC155, recovered 25 days apart from a hospitalized patient with sequential urinary and bloodstream infection. Both belonged to sequence type 361 (ST361), phylogroup A, serotype O-nontypeable:H30, and were separated by only 28 core-genome SNPs, confirming clonal relatedness. Despite this, the isolates differed sharply in carbapenemase content. CAEC145 carried blaOXA-1207, a recently described OXA-48-family variant, on a conjugative IncFII(pCoo)/ColKP3 plasmid, whereas CAEC155 lacked this determinant and instead harbored blaNDM-4 on a conserved IncX3 plasmid nearly identical to pJEG027, a member of a globally disseminated IncX3 lineage. This genotypic shift tracked a clear phenotypic transition. CAEC145 remained susceptible to imipenem and meropenem while resistant to ertapenem, whereas CAEC155 showed uniform high-level resistance to all three carbapenems and to ceftazidime-avibactam. Both isolates, however, remained susceptible to imipenem-relebactam, meropenem-vaborbactam, and cefiderocol. Comparative genomics linked the blaOXA-1207 element to a ΔTn6361 transposon structure also found in the original German isolates where blaOXA-1207 was first described, and a 137-genome core-genome phylogeny placed both isolates within a globally disseminated ST361 lineage carrying multiple carbapenemase classes. These findings document, to our knowledge, the first within-host succession from an OXA-48-like to an NDM-type carbapenemase during a single sequential E. coli infection, driven by plasmid-level displacement rather than in-place gene evolution, with implications for genomic surveillance and antibiotic selection.</jats:p>