Abstract: Objective　To explore the temporal association between resistance of Enterobacteriaceae and antibiotics consumption and to provide references for optimizing clinical antibiotics selection. Methods　By means of retrospective survey, we collected the antibiotic consumptions and the resistance rates of Klebsiella pnenmoniae and Escherichia coli against piperacillin/tazobactam, meropenem, and imipenem at Lianyungang First People's Hospital from January 2016 to December 2021. Linear regression analysis was used to evaluate the trends of quarterly consumptions of antibiotic prescriptions and antimicrobial resistance during the study period. Cross-correlation function analyses were used to determine the temporal correlation between the quarterly isolation proportion of antibiotic consumption and resistance rate in each quarter. Results　During the 6 years, the resistance rates of Klebsiella pnenmoniae against piperacillin-tazobactam (P<0.001) and meropenem (P=0.001) increased over the 6 years period, while the resistance rate of Escherichia coli against piperacillin/tazobactam gradually decreased (P<0.001). The consumption of carbapenems showed an increasing trend (P=0.008), while the consumption of β-lactam antibiotics was decreasing (P=0.032). The resistance rate of Klebsiella pnenmoniae against piperacillin/tazobactam increased with carbapenem consumption (r=0.812, Lag=0, P=0.022), and the resistance rates of Klebsiella pnenmoniae against meropenem (r=0.704, Lag=1, P=0.037) and imipenem (r=0.885, Lag=1, P=0.005) positively correlated with carbapenem consumption. The consumption of β-lactam antibiotics positively correlated with the resistance rates of Escherichia coli (r=0.587, Lag=3, P=0.045) and Klebsiella pnenmoniae (r=0.531, Lag=2, P=0.039) against piperacillin/tazobactam. Conclusions　There is certain temporal correlation between antibiotic usage and resistance in Enterobacteriaceae. And it is necessary for the hospital to optimize the selection of antibiotics so as to curb the progress of resistance of Enterobacteriaceae.

Key words: Temporal association, Resistance, Antibiotics, Antibiotics consumption

摘要： 目的　探讨肠杆菌科细菌耐药性与抗菌药物使用强度时间相关性，为优化抗菌药物临床选用提供依据。方法　采用回顾性调查方法，统计连云港市第一人民医院2016年1月至2021年12月期间住院患者各类标本中检出肺炎克雷伯菌、大肠埃希菌对哌拉西林/他唑巴坦、美罗培南以及亚胺培南耐药率和同期β‐内酰胺酶复合制剂、碳青霉烯类抗菌药物使用强度。采用线性回归分析抗菌药物季度使用强度和细菌季度耐药率变化趋势，运用互相关函数分析抗菌药物季度使用强度与细菌季度耐药率之间时间相关性。结果　6年期间肺炎克雷伯菌对哌拉西林/他唑巴坦（P<0.001）、美罗培南（P=0.001）耐药率均呈上升趋势，大肠埃希菌对哌拉西林/他唑巴坦耐药率逐渐下降（P<0.001）。研究期间碳青霉烯类抗菌药物使用强度呈上升趋势（P=0.008），β-内酰胺酶复合制剂类抗菌药物使用强度呈下降趋势（P=0.032）。肺炎克雷伯菌对哌拉西林/他唑巴坦耐药率与碳青霉烯类抗菌药物使用强度高度同步（r=0.812，Lag=0，P=0.022），对美罗培南（r=0.704，Lag=1，P=0.037）和亚胺培南（r=0.885，Lag=1，P=0.005）耐药率与碳青霉烯类抗菌药物使用强度均呈显著正相关。β-内酰胺酶复合制剂类抗菌药物使用强度与大肠埃希菌（r=0.587，Lag=3，P=0.045）和肺炎克雷伯菌（r=0.531，Lag=2，P=0.039）对哌拉西林/他唑巴坦耐药率均呈正相关。结论　医院肠杆菌科细菌耐药率与抗菌药物使用强度存在一定时间相关性，临床应优化抗菌药物合理选用，遏制肠杆菌科细菌耐药性进展。

关键词: 时间相关性, 细菌耐药性, 抗菌药物, 使用强度