Antimicrobial Use and Carbapenem-Resistant Enterobacterales in Korea: A Nationwide Case-Control Study With Propensity Score Matching

Background: Nationwide research on the association between carbapenem-resistant Enterobacterales (CREs) and antibiotic use is limited. Methods: This nested case-control study analyzed Korean National Health Insurance claims data from April 2017 to April 2019. Based on the occurrence of CRE, hospitalized patients aged ≥ 18 years were classified into CRE (cases) and control groups. Propensity scores based on age, sex, modified Charlson comorbidity score, insurance type, long-term care facility, intensive care unit stay, and acquisition of vancomycin-resistant Enterococci were used to match the case and control groups (1:3). Results: After matching, the study included 6,476 participants (1,619 cases and 4,857 controls). Multivariable logistic regression analysis revealed that the utilization of broad-spectrum antibiotics, such as piperacillin/tazobactam (adjusted odds ratio [aOR], 2.178; 95% confidence interval [CI], 1.829–2.594), third/fourth generation cephalosporins (aOR, 1.764; 95% CI, 1.514–2.056), and carbapenems (aOR, 1.775; 95% CI, 1.454–2.165), as well as the presence of comorbidities (diabetes [aOR, 1.237; 95% CI, 1.061–1.443], hemiplegia or paraplegia [aOR, 1.370; 95% CI, 1.119–1.679], kidney disease [aOR, 1.312; 95% CI, 1.105–1.559], and liver disease [aOR, 1.431; 95% CI, 1.073–1.908]), were significantly associated with the development of CRE. Additionally, the CRE group had higher mortality (8.33 vs. 3.32 incidence rate per 100 person-months, P < 0.001) and a total cost of healthcare utilization per person-month (15,325,491 ± 23,587,378 vs. 5,263,373 ± 14,070,118 KRW, P < 0.001) than the control group. Conclusion: The utilization of broad-spectrum antibiotics and the presence of comorbidities are associated with increasing development of CRE. This study emphasizes the importance of antimicrobial stewardship in reducing broad-spectrum antibiotic use and CRE disease burden in Korea.