Antibiotic stewardship is a multidisciplinary, evidence-based approach to optimize antibiotic use and mitigate development of antibiotic resistance. Neonates have high rates of antibiotic exposure, particularly those born preterm and admitted to the NICU, and mounting evidence describes the adverse consequences of such exposures in the absence of infection. Here, we review the general principles of antibiotic stewardship and how they can be applied in NICUs. The unique characteristics of NICUs and patients cared for in this setting, which warrant unique implementation strategies and special considerations are discussed. We summarize current antibiotic use metrics for assessment of responses to stewardship interventions and changes over time, and review evidence-based infection prevention practices in the NICU. Current recommendations for empiric antibiotic use in the NICU and the utility of infection biomarkers are summarized. Lastly, given the growing global threat of increasing antibiotic resistance, specific threats in the NICU are highlighted.
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