A Nonlinear Time-Series Analysis to Identify the Thresholds in Relationships Between Antimicrobial Consumption and Resistance in a Chinese Tertiary Hospital

Balancing the benefits and risks of antimicrobials in health care requires an understanding of their effects on antimicrobial resistance at the population scale. Therefore, we aimed to investigate the association between the population antibiotics use and resistance rates and further identify their critical thresholds.Data for monthly consumption of six antibiotics (daily defined doses [DDDs]/1000 inpatient-days) and the number of cases caused by five common drug-resistant bacteria (occupied bed days [OBDs]/10,000 inpatient-days) from inpatients during 2009-2020 were retrieved from the electronic prescription system at Nanjing Drum Tower Hospital, a tertiary hospital in Jiangsu Province, China. Then, a nonlinear time series analysis method, named generalized additive models (GAM), was applied to analyze the pairwise relationships and thresholds of these antibiotic consumption and resistance.The incidence densities of carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Klebsiella pneumoniae (CRKP), and aminoglycoside-resistant Pseudomonas aeruginosa were all strongly synchronized with recent hospital use of carbapenems and glycopeptides. Besides, the prevalence of carbapenem-resistant Escherichia coli was also highly connected the consumption of carbapenems and fluoroquinolones. To lessen resistance, we determined a threshold for carbapenem and glycopeptide usage, where the maximum consumption should not exceed 31.042 and 25.152 DDDs per 1000 OBDs, respectively; however, the thresholds of fluoroquinolones, third-generation cephalosporin, aminoglycosides, and β-lactams have not been identified.The inappropriate usage of carbapenems and glycopeptides was proved to drive the incidence of common drug-resistant bacteria in hospitals. Nonlinear time series analysis provided an efficient and simple way to determine the thresholds of these antibiotics, which could provide population-specific quantitative targets for antibiotic stewardship.