Clonal OmpK35 truncation and incomplete genotype-phenotype correlation underlie cefiderocol resistance in carbapenem-resistant, hypervirulent Klebsiella pneumoniae from Romania

Purpose. Convergence of carbapenem resistance and hypervirulence in Klebsiella pneumoniae is an emerging global threat, historically described almost exclusively in hospital inpatients. We characterised the genomic epidemiology, resistance determinants and cefiderocol-resistance mechanisms of K. pneumoniae isolated from patients with documented prior hospital exposure, including outpatients, at a Romanian tertiary-care institution. Methods. Twenty-five clinical K. pneumoniae isolates collected between August 2023 and July 2025 underwent long-read (Oxford Nanopore) whole-genome sequencing, Kleborate-based typing and resistance/virulence scoring, average nucleotide identity (ANI)-based clonality analysis, core-genome SNP comparison against a concurrent Romanian inpatient collection, and targeted BLAST-based screening of the porins OmpK35/OmpK36 and the siderophore receptors CirA/FyuA for loss-of-function variation underlying cefiderocol resistance. Results. Kleborate resolved seven sequence types; ST383 (n = 12) and ST101 (n = 8) accounted for 80% of isolates. NDM (n = 16: NDM-5, n = 10, ST383-restricted; NDM-1, n = 6) and OXA-48 (n = 11) were the dominant carbapenemases; nine isolates co-carried an NDM variant with OXA-48. Eight ST383 isolates carried the aerobactin locus ( iuc ) and scored 3 on the Kleborate virulence scale, meeting criteria for convergent carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKp); all eight also carried armA , a 16S rRNA methyltransferase conferring pan-aminoglycoside resistance, absent from all 17 aerobactin-negative isolates. All 25 isolates were cefiderocol-resistant by EUCAST criteria (MIC 4–32 mg/L) yet remained susceptible to aztreonam-avibactam. NDM carriage and OmpK35 truncation each trended toward higher cefiderocol MIC, but genotype did not predict MIC deterministically: isolates genotypically identical at every screened locus differed up to four-fold in MIC. The OmpK35 truncation was clonally inherited across all eight ST101 isolates but arose independently at least twice within ST383. Immune-chromatographic carbapenemase testing was discordant with WGS in 4/25 (16%) isolates. Core-SNP analysis against a concurrent 101-isolate inpatient collection identified seven ST383 pairs within a 20-SNP transmission threshold. Conclusions. A convergent, cefiderocol-resistant CR-hvKp ST383 lineage circulates across outpatient and inpatient settings in Romania, with clonal aminoglycoside co-resistance and heterogeneous, only partially genotype-predictable cefiderocol resistance. These findings support extending genomic surveillance beyond acute inpatient care.