Within-patient carbapenem heteroresistance in klebsiella pneumoniae associated with a repeat-associated blaNDM-1 resistance-module deletion

Carbapenem resistance is often treated as a stable clinical phenotype, although plasmid structural variation can generate closely related isolates with divergent susceptibility profiles. We investigated longitudinal Klebsiella pneumoniae isolates recovered from one patient during hospitalization. Resistant KP02 and KP03 and susceptible KP04 belonged to ST37/KL104; KP03 and KP04 were recovered from the same wound specimen and primary culture. Independent sequencing of three colonies from each isolate showed stable within-isolate genomic states and no mutually differing single-nucleotide polymorphisms in the shared callable core. The reassemble data sequences identified a 10,483-bp difference between the IncHI1B/IncFIB(K) multireplicon plasmids Pkp02_1 and Pkp04_1. The interval was delimited by two identical direct repeats containing sul1 and qacEΔ1 , and read-level validation, an independent assembly, and structural PCR supported a repeat-associated deletion. An outward-facing PCR product was compatible with a candidate circular intermediate, although its complete circular sequence and abundance remain unresolved. Under antibiotic-free conditions, the module-lacking isolate showed higher growth and final biomass; this association was not assigned uniquely to the deleted module. This single-patient study provides a clinically grounded, hypothesis-generating model for how repeat-associated plasmid rearrangements may contribute to carbapenem phenotypic heterogeneity.