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The core strategies recommended for antimicrobial stewardship programs, formulary restriction with preauthorization and prospective audit and feedback, can be difficult to implement with limited resources; therefore, we took an approach of guideline development and education with the goal of reducing overall antibiotic use and unwarranted use of broad-spectrum antimicrobials.Retrospective chart review before and after intervention.Le Bonheur Children’s Hospital pediatric, neonatal, and cardiac ICUs.All patients in our pediatric, neonatal, and cardiac ICUs within the time frame of the study.Baseline review in our ICUs revealed excessive use of broad-spectrum antibiotics and inconsistency in managing common pediatric infections. Guidelines were developed and implemented using cycles of education, retrospective review, and feedback. Purchasing and antibiotic use data were obtained to assess changes before and after guideline implementation. Unit-specific days of therapy were measured using periodic chart audit. Segmented regression analysis was used to assess changes in purchasing and broad-spectrum antibiotic days of therapy. The change in median monthly purchases was assessed using 2-tail Student t test.Hospital-wide targeted broad-spectrum antibiotic days of therapy/1,000 patient-days during the preimplementation year averaged 105 per month and decreased 33% to 70 per month during the postimplementation year. The overall antibiotic days of therapy decreased 41%, 21%, and 18%, and targeted broad-spectrum antibiotic days of therapy decreased by 99%, 75%, and 61% in the cardiac, pediatric, and neonatal ICUs, respectively, after guideline implementation. Yearly purchases of our most common broad-spectrum antibiotics decreased 62% from $230,059 to $86,887 after guideline implementation. Median monthly purchases of these drugs before implementation were $19,389 and $11,043 after implementation (p < 0.001).Guideline implementation was successful in reducing targeted broad-spectrum antibiotic use and acquisition cost. Programs with very limited resources may find similar implementation of guidelines effective to provide initial success, so that putting into practice one of the more resource intensive core strategies, such as prospective audit and feedback, may be feasible.