A multifaceted approach with four parallel strategies including infection prevention, accurate, prompt diagnosis and treatment, prudent use of antimicrobials, and prevention of transmission is required to reduce antimicrobial resistance in hospitals. As the exclusive use of a specific antibiotic causes resistance of microorganisms to it, balanced use of different antimicrobials is mandatory to reduce the selection pressure. In Hyogo College of Medicine, an antimicrobial stewardship program led by physicians and pharmacists facilitates hospital-wide heterogeneous antibiotic usage and has been associated with significant reductions in the isolation of multiple drug-resistant (MDR) organisms. To prevent the transmission of MDR organisms, standard precautions and transmission-based precautions should be enforced by infection control nurses. The establishment of a surveillance system for MDR organisms by laboratory personnel is important for the immediate intervention by the infection control team. In an infectious outbreak by MDR organisms, a multidisciplinary approach is necessary, and outbreaks of carbapenem-resistant Enterobacteriaceae infections in our institution were controlled with the support of the facility administration division.