Exploring thresholds and interaction effects among antibiotic usage, covariates, and their effect on antibiotic resistance using an extended-spectrum ß-Lactamase-producing Klebsiella pneumoniae case.

BACKGROUND: 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 ß-lactamase-producing Klebsiella pneumoniae (ESBL-producing K. pneumoniae) in hospitalized patients. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Identifying Targets for Antibiotic Use for the Management of Carbapenem-Resistant Acinetobacter baumannii (CRAb) in Hospitals-A Multi-Centre Nonlinear Time-Series Study.

Solutions are needed to inform antimicrobial stewardship (AMS) regarding balancing the access to effective antimicrobials with the need to control antimicrobial resistance. Theoretical and mathematical models suggest a non-linear relationship between antibiotic use and resistance, indicating the existence of thresholds of antibiotic use beyond which resistance would be triggered. It is anticipated that thresholds may vary across populations depending on host, environment, and organism factors. Further research is needed to evaluate thresholds in antibiotic use for a specific pathogen across different settings. The objective of this study is to identify thresholds of population antibiotic use associated with the incidence of carbapenem-resistant Acinetobacter baumannii (CRAb) across six hospital sites in Oman. The study was an ecological, multi-centre evaluation that involved collecting historical antibiotic use and CRAb incidence over the period from January 2015 to December 2019. By using non-linear time-series analysis, we identified different thresholds in the use of third-generation cephalosporins, piperacillin-tazobactam, aminoglycoside, and fluoroquinolones across participating hospitals. The identification of different thresholds emphasises the need for tailored analysis based on modelling data from each hospital. The determined thresholds can be used to set targets for each hospital AMS, providing a balance between access to these antibiotics versus controlling CRAb incidence.