At the Kobe University Hospital, we have been conducting weekly multidisciplinary prospective audit and feedback since March 2009 to optimize antimicrobial use. However, daily immediate interventions after the initiation of antimicrobial therapy have not been sufficiently implemented. Therefore, a full-time pharmacist specializing in antimicrobial therapy joined the newly launched antimicrobial stewardship team in May 2018, and started daily monitoring to optimize the use of broad-spectrum antimicrobials, such as antipseudomonal antibiotics and anti-MRSA agents. For the medical staff to better understand antimicrobial therapy, the educational lectures were conducted four times after intervention. This study aimed to evaluate the impact of a full-time pharmacist’s intervention on antimicrobial stewardship. The effects before the intervention period (May–December 2017) and after the intervention period (May–December 2018) on antibiotic therapy and clinical outcomes were compared. The rate of blood collection for culture before starting broad-spectrum antibiotics significantly increased after intervention (71% vs. 83%, p < 0.001), and initially prescribed broad-spectrum antibiotics were significantly de-escalated (55% vs. 80%, p = 0.002). A significant reduction in the monthly use of antipseudomonal antibiotics was observed (50.5 vs. 41.6 defined daily doses per 1,000 patient-days, p = 0.012). The incidence of hospital-acquired Clostridioides difficile infection (HA-CDI) significantly decreased after intervention (0.11 vs. 0.054 cases per 1,000 patient-days, p = 0.033). The 30-day mortality rate did not change between the two periods (19% vs. 17%, p = 0.4). Our intervention ensured appropriate antimicrobial therapy and reduced the incidence of HA-CDI without worsening the clinical outcomes.