Antibiotic Use Thresholds for Carbapenem-Resistant Gram-Negative Bacteria: A Nonlinear Time-Series Study

To study the association between antimicrobial use density (AUD) and carbapenem-resistant gram-negative bacteria (CRGN) detection rate in a Hospital from 2015 to 2023 and to determine the critical threshold for antimicrobial drug use.

The consumption of antibiotics and the detection rates of four CRGN from inpatients were obtained on quarterly. Regression discontinuity design was used to determine the effect of antibiotics on the detection rates of CRGN. Nonlinear time-series analysis with generalized additivity models (GAMs) was applied. A P value of <0.05 and the adjusted R² value of >0.3 were considered statistically significant.

The consumption of antibiotics remained stable from 2015 to 2019, then showed a decreasing trend from the first quarter of 2020 to the first quarter of 2021, subsequently showed a gradual increasing trend from the second quarter of 2021 to the fourth quarter of 2023. The detection rate of carbapenem-resistant Acinetobacter baumannii (CRAB) exceeded 50% from the first quarter of 2015 to the second quarter of 2019, even above 90% from the fourth quarter of 2018 to the second quarter of 2019, then the rate gradually decreased. The detection rates of carbapenem-resistant Klebsiella pneumoniae (CRKP) and Carbapenem-resistant Pseudomonas aeruginosa (CRPA) both showed increasing trend from the first quarter of 2015 to the second quarter of 2019, while showed gradual decreasing trend from the fourth quarter of 2019 to the third quarter of 2023. We found that the detection rates of CRGN were significantly associated with the consumption of carbapenems, aminoglycosides, fluoroquinolones, and glycopeptides (lag coefficient [1-3], P < 0.05, adjusted R² [0.347-0.808]).

AUD is associated with the detection rates of CRGN. To reduce the detection rates of CRGN, we determined thresholds for carbapenems, aminoglycosides, fluoroquinolones, and glycopeptides at 5.82, 0.06, 7.09, and 0.77 Defined Daily Doses (DDDs)/(100 patient-days), respectively.