📖 ABSTRACT/OVERVIEW
Multidrug-resistant Enterobacteriaceae, including carbapenem-resistant and extended-spectrum beta-lactamase-producing strains, represent an escalating public health catastrophe in Nigerian tertiary hospitals, yet molecular epidemiological data characterizing the genetic diversity and transmission dynamics of these organisms remain fragmented. This study conducted a multi-site cross-zonal molecular epidemiological investigation of multidrug-resistant Enterobacteriaceae isolated from tertiary hospitals across four geopolitical zones in Nigeria. Clinical isolates of Escherichia coli and Klebsiella pneumoniae from blood, urine, and wound cultures were collected from six tertiary hospitals in Lagos, Kano, Enugu, Maiduguri, Benin City, and Abuja over 24 months. Whole-genome sequencing was performed on 480 selected isolates to characterize resistance genes, plasmid replicons, sequence types, and phylogenetic relationships. The bla-NDM carbapenemase gene was identified in 18 percent of Klebsiella pneumoniae and 9 percent of Escherichia coli isolates. Phylogenomic analysis revealed high-risk international clonal lineages including sequence type 131 in Escherichia coli and sequence type 258 in Klebsiella pneumoniae, suggesting importation and nosocomial spread. Horizontal gene transfer via conjugative plasmids was identified as the primary resistance dissemination mechanism. Significant inter-hospital clonal relatedness across zones indicated potential healthcare-network transmission. These findings provide the most comprehensive genomic resistance dataset from Nigerian hospitals to date and establish the biological foundation for evidence-based infection prevention and antibiotic stewardship policies at the national level. Keywords: antimicrobial resistance, multidrug-resistant Enterobacteriaceae, whole-genome sequencing, molecular epidemiology, Nigeria
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