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Rural hospitals of <100 occupied bed days benefit from new antimicrobial stewardship.Dramatically decreased Clostridium difficile infection rates occurred in 1 year.Annualized drug cost savings was $280,000.Total antibiotic utilization declined by 10%.Total targeted antimicrobial costs decreased by 50%.New Joint Commission antimicrobial stewardship requirements took effect on January 1, 2017, promoted as a central strategy for coping with the emerging problems of antimicrobial resistance and Clostridium difficile infection. Our objective was to measure the effects of a new antimicrobial stewardship program (ASP) in a rural community hospital with no prior ASP, in the context of having a new infectious disease specialist on staff.An ASP team was formed to implement a prospective audit with health care provider feedback and targeting 12 antimicrobial agents in a rural hospital in Georgia. An educational grand rounds lecture series was provided before implementation of the ASP to all prescribers. After implementation, algorithms to aid the selection of empirical antibiotics for specific infectious disease syndromes based on local antibiograms were provided to prescribers to improve this selection. Rates of C difficile infections, total targeted antimicrobial costs, and drug utilization rates were calculated for 1 year pre-ASP implementation (2013) and 1 year post-ASP implementation (October 2014-December 2015).The patient safety metric of C difficile infections decreased from 3.35 cases per 1,000 occupied bed days (OBDs) in 2013 to 1.35 cases per 1,000 OBDs in 2015. Total targeted antimicrobial costs decreased 50% from $16.93 per patient day in 2013 to $8.44 per patient day in 2015. Overall antimicrobial use decreased 10% from before the ASP initiative to 1 year after it. Annualized savings were $280,000 in 1 year, based on drug savings only.Judicious use of antimicrobials and resources can improve a patient safety metric and decrease costs dramatically in rural institutions where the average hospital census is <100 patients per day. The savings would allow the institutions to spend better while improving the use of antimicrobials.