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Objectives: The objective of this study was to assess the antimicrobial resistance (AMR) landscape and the impact of COVID-19 on AMR in Egypt, Iraq, Jordan, and Lebanon, and to gather expert opinions on the barriers to the implementation of antimicrobial stewardship (AMS) initiatives in the region. Methods: A cross-sectional questionnaire survey was used to assess the current AMR landscape, existing AMS initiatives, barriers to implementing AMS initiatives, and the impact of COVID-19 on AMR in the four countries. Results: The survey was completed by 204 physicians from Egypt (n = 82), Lebanon (n = 49), Iraq (n = 43), and Jordan (n = 30). Previous antibiotic use and previous bacterial colonization were perceived as the most common risk factors for an increase in AMR. According to the survey, multidrug-resistant (MDR) gram-negative bacteria were most common in lower respiratory tract infections, and Klebsiella pneumoniae and Escherichia coli were the most commonly identified gram-negative bacteria in hospital-acquired infections. Only 14.8% of pediatric physicians and 28.6% of adult physicians reported that target pathogen genotyping and phenotyping were done in hospitals, and the most commonly reported reasons for the lack of testing were technological and resource constraints. These constraints, coupled with the scarcity and high cost of newer antibiotics, have been identified as the most significant barriers to the successful management of MDR gram-negative bacterial infections in the region. It was reported that the spectrum of activity and safety of the antibiotic, the site of infection, the presence of comorbidities, and published guidelines and local antibiograms determined the choice of empirical antibiotic therapy for patients in the region. The four countries experienced a significant rise in AMR due to several factors during the COVID-19 pandemic, including an increase in hospital occupancy, a shift in priorities away from AMR surveillance, and changes in AMR epidemiology. Additionally, the large volumes of unnecessary and unsubstantiated antibiotic prescriptions during the COVID-19 pandemic has led to subsequent antibiotic shortages and significant increases in AMR in the region. Physicians also noted that the majority of COVID-19 patients were already on antibiotics before visiting the healthcare facility. MDR gram-negative bacteria were found in the majority of COVID-19 patients admitted to the intensive care unit. Despite the fact that various AMS initiatives have been implemented, they are not standardized across the region. Some of the main barriers to AMS implementation in the region are a lack of adequately trained AMS staff, lack of AMS knowledge and training among healthcare professionals, financial constraints, and the lack of AMR surveillance systems. Conclusion: These survey results provide valuable insights into the existing AMR and AMS landscape in the region, as well as the barriers that impede efficient AMS and AMR management. Based on these findings, the authors developed a call to action that suggests ways for each country in the region to address these challenges. [ABSTRACT FROM AUTHOR]