Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) emergence and dissemination, is an important healthcare concern due to its limited therapeutic options. Ceftazidime/avibactam (CAZ/AVI) is a recently approved antibiotic combination that may be effective in treating these resistant infections. The aim of the current study was to determine the prevalence of CRKP among clinical isolates from neonatal intensive care unit (NICU) and to evaluate the in-vitro activity of CAZ/AVI against them. Methods: A total of 255 clinical samples were collected from neonates with suspected sepsis. All Klebsiella pneumoniae isolates were identified by standard methods. Antibiotic susceptibility testing, screening for Extended-spectrum β lactamase (ESBL) production, carbapenem resistance, carbapenemase production and susceptibility to CAZ/AVI were done according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Of the 255 neonates clinically suspected as neonatal sepsis, only 136 (53.3%) had positive culture results, out the 136 culture-proven cases, 72 (52.9%) were positive for Klebsiella pneumoniae, of them ESBL producers were 92% (n=66) and CRKP were 32% of isolates (n=23). All of the CRKP were carbapenamase producers (39% serine-type and 61% metallo-β-lactamases (MBL) type). Serine carbapenamase and MBL producers showed high resistance against CAZ/AVI with a percentage of 77.8% and 100% respectively. Conclusion: The prevalence of CRKP is alarming in our NICU especially in the presesnce of neonatal risk factors like; neutropropenia, central line fixation and premature rapture of membranes. Ceftazidime/avibactam is an unsuitable option for the treatment of this type of resistant bacteria because of its high resistance