Klebsiella pneumoniae is notorious for causing healthcare-associated infections, which become more complicated by the acquisition of bla _NDM genes via mobile genetic elements. Although Pakistan is a well-established hot spot of bla _NDM -positive K. pneumoniae , detailed molecular descriptions of bla _NDM -carrying plasmids are scarce. Seven K. pneumoniae isolates harboring bla _NDM were recovered from clinical sample sources during a 6 month period and tested for antimicrobial susceptibility. A long-read approach was used for whole-genome sequencing to obtain circularized plasmids and chromosomes for typing, annotation, and comparative analysis. The isolates were susceptible to colistin and tigecycline only among the tested antibiotics. We identified five sequence types (STs): ST11, ST16, ST716, ST464, and ST2856. Notably, three strains possessed the hypervirulent capsule KL2, while five were classified as O locus type O2a. Evidence of genetic diversity was further highlighted by the presence of four IncC plasmids harboring bla _NDM-1 , two IncX3 plasmids harboring bla _NDM-5 , and a single hybrid IncFIB/IncHI1B plasmid harboring bla _NDM-7 . These plasmids also carried additional antimicrobial resistance (AMR) genes conferring resistance to aminoglycosides, cephalosporins, and fluoroquinolones. We identified the plasmidome of the K. pneumoniae isolates and characterized the New Delhi metallo-beta-lactamase (NDM)-carrying plasmids. Genetic analysis confirmed the presence of bla _NDM-1 and bla _NDM-5 on broad host range plasmids and bla _{NDM- 7} in a previously unreported hybrid plasmid backbone. We emphasized the critical role of plasmids in spreading bla _NDM in the clinical setting in Pakistan. Hence, we stressed the urgent need for enhanced surveillance, not least in low-middle income countries, infection control measures, and adherence to the "Access," "Watch," and "Reserve" guidelines in antibiotics use.

Importance: Infections caused by NDM-producing Klebsiella pneumoniae are a significant challenge to treat and represent a crucial health burden in low- and middle-income countries (LMICs). Most of the bla _NDM are located on plasmids that promote horizontal gene transfer. However, there is a lack of comprehensive information on the genetic context of the NDM-carrying plasmids in Pakistan. This study presents a detailed analysis of seven NDM-plasmids in clinical K. pneumoniae isolates, shedding light on their high-risk sequence types and multiple resistance determinants. We also describe the plasmid-bearing NDM alleles (bla _NDM-1 , bla _NDM-5 , and bla _NDM-7 ). Notably, we are the first to report bla _NDM-7 on the hybrid IncFIB/IncHI1B backbone in Pakistan, a plasmid that has rarely been reported previously globally. Understanding the plasmid genomic landscape is paramount to comprehensively understanding the AMR scenario in this LMIC.