Genome-resolved analysis of multidrug-resistant ESKAPE pathogens reveals Klebsiella pneumoniae diversity and plasmid-mediated resistance in a patient in intensive care.

Multidrug-resistant (MDR) Gram-negative pathogens continue to threaten patient outcomes in intensive care units (ICUs) worldwide, particularly in regions where genomic surveillance is limited. Understanding intra-host genomic diversity and mobility of resistance determinants remain essential for mitigating global antimicrobial resistance (AMR) threats. Whole genome sequencing and molecular analysis were performed on three selected isolates to identify resistance and virulence determinants. The isolates exhibited complex and heterogenous resistomes shaped by extensive antimicrobial exposure during prolonged ICU care. Two genetically distinct Klebsiella pneumoniae strains (ST11 and ST15) demonstrating intra-patient strain diversity, an emerging trend in high-risk clinical settings globally, along with an Acinetobacter baumannii strain (ST944) were recovered from the same patient. Key resistance genes linked to mobile genetic elements (MGEs) were identified, including blaCTX-M-15 and blaNDM-5 in K. pneumoniae ST11 and blaADC-152 in A. baumannii. A plasmid-associated contig harbouring blaDHA-1 and qnr resistance genes represented a 'high-risk' mobile platform with international similarity in K. pneumoniae, highlighting the global circulation of resistance plasmids. Virulence profiling revealed conserved and unique determinants, including biofilm, siderophore, and secretion loci, with one isolate carrying a complete Yersiniabactin locus associated with MGEs. This study provides the first genome-resolved case from the Caribbean demonstrating intra-host co-existence of globally important MDR lineages and plasmid-mediated dissemination of key resistance genes. Within the global AMR challenge, this analysis offers novel insight into the convergence of resistance and virulence traits and highlights the value of localized genomic surveillance in understanding pathogen adaptation, mobility, and persistence under high antimicrobial pressure. These findings emphasize the importance of incorporating genomic data from diverse geographic regions into global AMR networks to better manage MDR ESKAPE pathogens in ICU environments.