At secondary healthcare, Carbapenem-Resistant Enterobacterales (CREs) such as observed in Klebsiella pneumoniae are a global public health priority with significant clinical outcomes. In this study, we describe clinical, phenotypic, and genotypic characteristics of three pan-drug resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for acquisition of multidrug resistant organisms while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents such as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria including CREs pointing towards potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types as well as a mutated outer membrane porin protein (OmpK37).