Correlation between Antimicrobial Resistance and the Hospital-Wide Diverse Use of Broad-Spectrum Antibiotics by the Antimicrobial Stewardship Program in Japan

Increased antibiotic use and antibiotic homogeneity cause selective pressure. This study investigated the correlation between antibiotic diversity and antimicrobial resistance (AMR) in Gram-negative organisms. The days of therapy/100 patient-days (DOT) for four broad-spectrum antibiotic classes were evaluated for 2015–2022. The antibiotic heterogeneity index (AHI) for the equal use of four classes (25%) and the modified AHI for the equal use of three classes (30%), excluding fluoroquinolones (10%), were measured (target: 1.0). Quarterly antibiotic use markers and the resistance rates against ≥2 anti-Pseudomonas antibiotics were compared. The DOT value was 9.94, and the relative DOT were 34.8% for carbapenems, 32.1% for piperacillin/tazobactam, 24.3% for fourth generation cephalosporins/ceftazidime/aztreonam, and 8.9% for fluoroquinolones. Although no correlation was found between the total DOT and the resistance rate for any bacterium, a significant negative correlation was found between the heterogeneity indices and resistance rates for Pseudomonas aeruginosa and Klebsiella pneumoniae. The significant cutoffs that discriminate the risk of resistance were 0.756 for the AHI and 0.889 for the modified AHI for K. pneumoniae. Antibiotic diversity is more important in preventing AMR than overall antibiotic use. The ideal ratio of broad-spectrum antibiotics should be studied for diversified use to prevent AMR.