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

Abstract

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.

Comparison of antibiotic use and antibiotic resistance between a community hospital and tertiary care hospital for evaluation of the antimicrobial stewardship program in Japan

“…The SAAR was developed by the CDC to provide a risk-adjusted benchmark of antibiotic use. Ueda et al [ 20 ] reported the SAAR of broad-spectrum antibiotics predominantly used for hospital-onset infections in a Japanese TCH. Between 2015 and 2022, the SAAR ranged from 1.10 to 1.82 in the ICU, from 0.50 to 1.03 in the department of respiratory medicine, and from 0.70 to 1.20 in the department of colorectal surgery.…”

“…Fluoroquinolones were used only in 12.5% of patients with bacteremia caused by difficult-to-treat gram-negative bacilli treated with broad-spectrum antibiotics in a Japanese hospital [ 30 ]. Recently, Ueda et al [ 20 ] reported that the % DOT values obtained in a rigorous 7-year AS program were 34.8% for carbapenems, 32.1% for piperacillin/tazobactam, 24.3% for fourth-generation cephalosporins/ceftazidime/aztreonam, and 8.9% for intravenous fluoroquinolones. From these results, a modified AHI for achieving a % DOT of 10% for fluoroquinolones and 30% for each of the remaining three broad-spectrum antibiotic classes was proposed, and an increased modified AHI value resulted in lower antibiotic resistant rates for P .…”

“…aeruginosa and K . pneumoniae [ 20 ]. The significant cutoff of the modified AHI to discriminate the risk of antibiotic resistance was 0.899 for K .…”

“…When 25% of the relative DOT in each antibiotic class is achieved, the AHI is 1. The modified AHI, which is a new indicator of balanced antibiotic use, was also calculated by defining a i as 0.1 for fluoroquinolones and 0.3 for each of the remaining three antibiotic class [ 20 ]. The modified AHI is the index when each antibiotic class (% DOT = 30%) except for fluoroquinolones (% DOT = 10%) is equally used.…”

“…In addition to the amount of antibiotic use, several authors have reported the usefulness of antibiotic diversity to prevent AMR [ 16 – 19 ]. Recently, Ueda et al [ 20 ] evaluated balanced use of broad-spectrum antibiotics using the antibiotic heterogeneity indices (AHIs). The authors found a negative correlation between the indices and rate of AMR in Pseudomonas aeruginosa and Klebsiella pneumoniae .…”