Genomic Characterisation of Carbapenem-Resistant Klebsiella pneumoniae Causing Neonatal Sepsis in Nigerian Tertiary Neonatal Units

Carbapenem-resistant Klebsiella pneumoniae is an urgent antimicrobial resistance threat responsible for untreatable neonatal sepsis outbreaks in tertiary neonatal units globally, and its molecular epidemiology in Nigeria's neonatal intensive care settings has not been characterised at genomic resolution. This study genomically characterises carbapenem-resistant K. pneumoniae isolates causing neonatal sepsis across eight tertiary neonatal units in four geopolitical zones over a 36-month prospective surveillance period. All blood culture K. pneumoniae isolates from neonates with sepsis undergo whole-genome sequencing using Illumina NextSeq. Carbapenemase gene content (OXA-48, KPC, NDM) is identified through CARD annotation. Multi-locus sequence typing defines clonal lineages, and core-genome phylogenetics using Parsnp reconstructs within- and between-unit transmission events. Environmental sampling of unit surfaces and healthcare worker hand cultures supplement clinical isolate data. Neonatal sepsis outcomes including 28-day mortality, organ dysfunction, and antibiotic susceptibility are recorded. The Antimicrobial Resistance Evolutionary Theory and Healthcare Transmission Dynamics Model provide the theoretical basis. Original contributions include the first multi-centre genomic surveillance study of CRKP neonatal sepsis in Nigeria, identifying high-risk transmission lineages and resistance gene reservoirs. Findings will directly inform NCDC antimicrobial resistance surveillance and neonatal unit infection control policy. Keywords: carbapenem-resistant Klebsiella pneumoniae, neonatal sepsis, whole-genome sequencing, antimicrobial resistance, Nigeria.