Background: Antibiotic resistance is a global issue that is rapidly spreading. The emergence of multi-drug resistant strains has been attributed to the overuse or misuse of antibiotics. Despite the lack of national data, the prevalence of multidrug resistant (MDR) bacteria in Egypt is comparable to or even higher than the global average. The US CDC defines carbapenem-resistant Enterobacteriaceae (CRE) as enterobacteria non-susceptible to any carbapenem or documented to produce a carbapenemase. Ceftazidime/Avibactam(CAZ/AVI) is a novel β-lactam and non-β-lactamase inhibitor with a distinct mechanism of action. The use of CAZ/AVI, compared with other sequential antibiotics including Colistin results in reduced mortality and less hospitalization time. Objective: The study aimed to compare the cost-effectiveness of Ceftazidime/Avibactam (CAZ/AVI) to Polymyxin E in treating carbapenem-resistant Enterobacteriaceae (CRE) infections in hospitalized adult patients in Egypt from the public payer perspective. Method: We used PubMed database for the search and only English-language papers were considered, with no restriction on publication date. Two independent reviewers performed the title and abstract screening, and a third principal reviewer resolved conflicts. All article titles and abstracts were initially screened using predefined exclusion criteria, such as no English abstract, no economic evaluation of an antibacterial agent, prevention strategies and non-transparent reporting of methodology. Based on the findings of the literature review, a decision tree model linked to a survival Markov model was developed to compare CAZ/AVI and Polymyxin E in hospitalized adult patients. The effectiveness measures were quality-adjusted life years (QALYs) and life years (Lys). From the public payer's perspective, costs in Egyptian health care settings were estimated. Deterministic and probabilistic sensitivity analyses were used to evaluate the model's robustness. Results: The discounted incremental QALYs associated with CAZ/AVI versus Colistin were 0.30, the life-years gained were 0.42 years, and the discounted incremental costs were EGP 51,528 over a five-year time horizon. These resulted in EGP 170,832 per QALY and EGP 121,473 per life-year gained. Conclusion: CAZ/AVI provides a breakthrough in the health benefit for CRE intensive care unit patients; however, it is not cost-effective against Colistin in the Egyptian health care settings at the current price level. Using a managed entry agreement could improve CAZ/AVI's cost-effectiveness and accessibility.