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

Mamoon A. Aldeyab, Zainab Said Al-Hashimy, Mubarak Al-Yaqoobi, Barbara R. Conway, Feras Darwish Elhajji, Stuart E. Bond, Elizabeth A. Lattyak, Syed Shahzad Hasan, William J. Lattyak

Research output: Contribution to journalArticlepeer-review


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 β-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.

Original languageEnglish
Pages (from-to)777-786
Number of pages10
JournalExpert Review of Anti-Infective Therapy
Issue number7
Early online date23 Jun 2023
Publication statusPublished - 1 Jul 2023

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