# Reducing the overall use of broad-spectrum antibiotics in NICU is associated with less prevalence of multi-drug resistant Klebsiella pneumoniae isolation in premature infants

## TL;DR

Reducing the use of broad-spectrum antibiotics in neonatal intensive care units is linked to fewer cases of multi-drug resistant Klebsiella pneumoniae in premature infants.

## Contribution

The study shows a direct link between antibiotic stewardship and reduced multi-drug resistance in Klebsiella pneumoniae in NICUs.

## Key findings

- Antibiotic use in the NICU dropped significantly from 2013 to 2022.
- The prevalence of multi-drug resistant Klebsiella pneumoniae decreased from 57.7% to 31.8% during the study period.
- Exposure to certain antibiotics increased the risk of multi-drug resistant Klebsiella pneumoniae.

## Abstract

The aim of this study was to evaluate the impact of an antibiotic stewardship program on the resistance profiles of Klebsiella pneumoniae (K. pneumoniae) in the neonatal intensive care unit (NICU). This was achieved by examining changes in the antimicrobial resistance patterns of K. pneumoniae isolates collected from preterm infants in a level 3 NICU between 2013 and 2022.

We examined antibiotic resistance patterns in all isolated K. pneumoniae strains cultured from preterm infants (gestational age < 37 weeks, postnatal age > 3 days) admitted to our NICU between 2013 and 2022. To assess temporal trends, we divided the study period into three phases (2013–2015, 2016–2018, and 2019–2022) to correlate antibiotic usage trends with resistance dynamics. Multivariable logistic regression was performed to identify risk factors associated with prevalence of multidrug-resistant (MDR) K. pneumoniae colonization or infection in the NICU.

Antimicrobial use, measured in defined daily doses(DDDs) per 100 patient-days, dropped sharply from 30.8 during 2013–2015 to 12.9 in 2016–2018, then fell further to 6.9 in 2019–2022. The rates of MDR K. pneumoniae isolation among all isolated K. pneumoniae strains decreased significantly from 57.7% in 2013–2015 to 31.8% in 2019–2022 (p = 0.001). The resistance rate to aztreonam declined from 60.8% during 2013–2015 to 41.0% in 2016–2018, then further decreased to 25.0% in 2019–2022. The resistance rate to cefepime decreased from 70.1% to 33.3% and finally to 10.2% across the same periods. The resistance rate to piperacillin-tazobactam declined significantly from 53.6% (2013–2015) to 15.2% (2016–2018) and further to 6.8% (2019–2022). The resistance rate to imipenem also declined from 51.5% (2013–2015) to 4.2% (2016–2018) and ultimately to 1.1% (2019–2022). Multivariable logistic regression analysis reveales that exposure to third-generation or higher cephalosporins (aOR = 2.460, 95%CI: 1.386 to 4.365, p = 0.002) or glycopeptide antibiotics (aOR = 1.887, 95%CI: 1.100 to 3.237, p = 0.021) prior to specimen collection increases the risk of isolating MDR K. pneumonia strains.

This study demonstrates that reducing broad-spectrum antibiotic use in NICUs may lower the prevalence of MDR K. pneumoniae colonization and infection in premature infants.