Phylogenetic analysis of bla NDM genes of carbapenem resistant uropathogens isolated from federal tertiary care hospital, Pakistan: insights into the evolution and dissemination of drug resistance

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Background and Objectives: Global health is seriously threatened by the rise of carbapenem-resistant Enterobacterales (CRE). The bla NDM gene, a key carbapenemase coding gene, causes global health concern due to its multidrug resistance and easy spread through mobile genetic elements. This study aimed to identify and genetically characterize the bla uropathogens, its antibiotic susceptibility, and its correlation with global sequences. NDM genes from Materials and Methods: Urine samples were processed following microbiological guidelines. Isolates were identified using API-20E. Antibiotic susceptibility was tested using disc diffusion method, and bacterial DNAs were extracted for bla gene sequencing for phylogenetic analysis. NDM Results: CREs were detected in 11.92% (n=51) of the 428 Enterobacterales. Among CRE isolates, 45% (n=23) were positive for bla NDM gene harbored by Klebsiella pneumoniae (57%), followed by Escherichia coli (26%). Uropathogenic CRE, har- boring bla , revealed susceptibility of 34.78%, 60.87%, and 65.22% to amikacin, nitrofurantoin, and fosfomycin respec- tively. The bla NDM-5 variant was most common (69.57%), followed by bla NDM-1 (26.09%) and bla NDM-7 (4.35%). Phylogenetic analysis revealed that bla NDM variants exhibit diverse relationships with Pakistani and worldwide sequences. Conclusion: The significant presence of bla NDM in uropathogens, along with extensive antibiotic resistance, underscores the urgent need for continuous monitoring and antibiotic stewardship programs to manage the growing threat of CRE infections.

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