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Introduction: Surgical site infections (SSIs) are one of the most frequently reported hospital acquired infections associated with significant spread of antibiotic resistance. Purpose: We aimed to evaluate a bundle-based approach in reducing SSI at acute surgical intensive care unit of the Emergency Hospital of Cairo University. Patients and Methods: Our prospective study ran from March 2018 to February 2019 and used risk assessment. The study was divided into three phases. Phase I: (pre-bundle phase) for 5 months; data collection, active surveillance of the SSIs, screening for OXA-48 producing Enterobacteriaceae and multidrug resistant Acinetobacter baumannii colonizers using Chrom agars were carried out. Phase II: (bundle-implementation) a 6-S bundle approach included education, training and postoperative bathing with Chlorhexidine Gluconate in collaboration with the infection control team. Finally, Phase III: (post-implementation) for estimation of compliance, rates of colonization, and infection. Results: Phase I encompassed 177 patients, while Phase III included 93 patients. A significant reduction of colonization from 24% to 15% (p< 0.001) was observed. Similarly, a decrease of SSI from 27% to 15% (p=0.02) was noticed. A logistic regression was performed to adjust for confounding in the implementation of the bundle and we found a 70% reduction of SSI odd's ratio (OR's ratio = 0.3) confidence interval (95% CI 0.14– 0.6) with significant Apache II (p=0.04), type of wound; type II (p=0.002), type III (p=0.001) and duration of surgery (p=0.04) as independent risk factors for SSI. Klebsiella pneumoniae was the most prevalent organism during phase I (34.7%). On the other hand, A. baumannii was the commonest organism to be isolated during phase III with (38.5%) preceding K. pneumoniae (30%). Conclusion: Our study demonstrated that the implementation of a multidisciplinary bundle containing evidence-based interventions was associated with a significant reduction of colonization and SSIs and was met with staff approval and acceptable compliance. [ABSTRACT FROM AUTHOR]