Abstract：
This study was aimed to explore thresholds with interaction effects among antibiotic usage, covariates (alcohol-based hand rub (ABHR)), and their effect on extended-spectrum β-lactamase-producing Klebsiella pneumoniae (ESBL-producing K. pneumoniae) in hospitalized patients.
Multivariate Adaptive Regression Spline models were used. These considered second-order interactions among antibiotic use and ABHR in addition to potential thresholds that further improve explained variance in the ESBL-producing K. pneumoniae response. The study involved collecting monthly hospital-level data for January 2017-December 2021.
Analysis of the main effects showed that third-generation cephalosporins above 2.00 DDD/100 occupied bed days (OBD) generally increased ESBL-producing K. pneumoniae incidence (cases/100 OBD). Levels of ABHR above 6.61 L/100 OBD were shown to generally decrease ESBL-producing K. pneumoniae incidence. Second-order interactions revealed that when third-generation cephalosporin use was greater than 3.71 DDD/100 OBD, and ABHR was greater than 6.6 L/100 OBD (same as main effect threshold), ABHR partially lost effectiveness in its ability to reduce ESBL-producing K. pneumoniae incidence. This demonstrates the importance of not exceeding the identified thresholds of 3.71 DDD/100 OBD for third-generation cephalosporin use.
The main-effect thresholds in third-generation cephalosporins and ABHR, and the identified interaction between third-generation cephalosporins and ABHR can inform effective hospital antimicrobial stewardship.
Multivariate Adaptive Regression Spline models were used. These considered second-order interactions among antibiotic use and ABHR in addition to potential thresholds that further improve explained variance in the ESBL-producing K. pneumoniae response. The study involved collecting monthly hospital-level data for January 2017-December 2021.
Analysis of the main effects showed that third-generation cephalosporins above 2.00 DDD/100 occupied bed days (OBD) generally increased ESBL-producing K. pneumoniae incidence (cases/100 OBD). Levels of ABHR above 6.61 L/100 OBD were shown to generally decrease ESBL-producing K. pneumoniae incidence. Second-order interactions revealed that when third-generation cephalosporin use was greater than 3.71 DDD/100 OBD, and ABHR was greater than 6.6 L/100 OBD (same as main effect threshold), ABHR partially lost effectiveness in its ability to reduce ESBL-producing K. pneumoniae incidence. This demonstrates the importance of not exceeding the identified thresholds of 3.71 DDD/100 OBD for third-generation cephalosporin use.
The main-effect thresholds in third-generation cephalosporins and ABHR, and the identified interaction between third-generation cephalosporins and ABHR can inform effective hospital antimicrobial stewardship.
摘要：
■本研究旨在探索抗生素使用之间相互作用效应的阈值，协变量（基于酒精的手擦（ABHR）），以及它们对住院患者产超广谱β-内酰胺酶肺炎克雷伯菌（产ESBL肺炎克雷伯菌）的影响。
■使用多元自适应回归样条模型。这些考虑了抗生素使用和ABHR之间的二阶相互作用，以及进一步改善产生ESBL的肺炎克雷伯菌反应的解释差异的潜在阈值。该研究涉及收集2017年1月至2021年12月的每月医院水平数据。
■对主要影响的分析表明，在2.00DDD/100占用床日（OBD）以上的第三代头孢菌素通常会增加产生ESBL的肺炎克雷伯菌的发病率（病例/100OBD）。显示高于6.61L/100OBD的ABHR水平通常降低产ESBL肺炎克雷伯菌的发病率。二阶相互作用表明，当第三代头孢菌素的使用大于3.71DDD/100OBD时，ABHR大于6.6L/100OBD（与主效应阈值相同），ABHR部分丧失了降低产ESBL肺炎克雷伯菌发病率的能力。这证明了第三代头孢菌素使用不超过3.71DDD/100OBD的确定阈值的重要性。
■第三代头孢菌素和ABHR的主效应阈值，第三代头孢菌素和ABHR之间确定的相互作用可以为有效的医院抗菌药物管理提供信息。
■使用多元自适应回归样条模型。这些考虑了抗生素使用和ABHR之间的二阶相互作用，以及进一步改善产生ESBL的肺炎克雷伯菌反应的解释差异的潜在阈值。该研究涉及收集2017年1月至2021年12月的每月医院水平数据。
■对主要影响的分析表明，在2.00DDD/100占用床日（OBD）以上的第三代头孢菌素通常会增加产生ESBL的肺炎克雷伯菌的发病率（病例/100OBD）。显示高于6.61L/100OBD的ABHR水平通常降低产ESBL肺炎克雷伯菌的发病率。二阶相互作用表明，当第三代头孢菌素的使用大于3.71DDD/100OBD时，ABHR大于6.6L/100OBD（与主效应阈值相同），ABHR部分丧失了降低产ESBL肺炎克雷伯菌发病率的能力。这证明了第三代头孢菌素使用不超过3.71DDD/100OBD的确定阈值的重要性。
■第三代头孢菌素和ABHR的主效应阈值，第三代头孢菌素和ABHR之间确定的相互作用可以为有效的医院抗菌药物管理提供信息。
