# Epidemiological Insights into Carbapenem-Resistant Enterobacterales Throughout the COVID-19 Pandemic in Buenos Aires, Argentina

## TL;DR

This study examines how antibiotic-resistant bacteria, specifically carbapenem-resistant Enterobacterales, evolved during the COVID-19 pandemic in Buenos Aires, Argentina.

## Contribution

The study reveals a shift in resistance patterns and the spread of specific carbapenemase-producing Klebsiella pneumoniae clones during the pandemic.

## Key findings

- CRE isolates showed a significant shift from multidrug-resistant to extensively drug-resistant phenotypes during the pandemic.
- blaKPC-2 and blaNDM-5 were the most prevalent carbapenemase alleles in Klebsiella pneumoniae.
- The CG258-tonB79 clone of Klebsiella pneumoniae became dominant in both hospitals by 2022.

## Abstract

Background: Carbapenem-resistant Enterobacterales (CRE) are a global public health concern, with carbapenem-resistant Klebsiella pneumoniae (CR-Kp) recognised as the highest-priority pathogen. This study aimed to investigate the epidemiological features of CRE isolates throughout the COVID-19 pandemic in Buenos Aires, Argentina. Methods: A prospective study was conducted in two hospitals from 2019 to 2022, recovering all CRE from inpatients. Antimicrobial susceptibility was performed by automated and/or manual tests, according to CLSI. β-lactamases detection was performed using Multiplex PCR and MALDI-TOF MS. Kp typing was assessed by multiplex PCR and/or MLST based on WGS. Results: 22% (359/1594) were CRE, predominantly CR-Kp. Overall, high non-susceptibility (NS) rates were observed in both centres. NS remained largely stable in HA, except for a significant increase in colistin NS, whereas HB showed a rise in NS to multiple antimicrobials over time. A significant shift from multidrug-resistant to extensively drug-resistant and difficult-to-treat phenotypes was observed across the study periods. Out of 359 CRE, blaKPC was confirmed in 141, blaNDM in 170, and blaKPC + blaNDM in 20 isolates. Before the COVID-19 pandemic, KPC was the main carbapenemase in HB, while NDM was already the prevalent one in HA. In 2022, both enzymes showed similar prevalence. blaKPC-2 and blaNDM-5 were the prevalent alleles in K. pneumoniae. Before the COVID-19 pandemic, K. pneumoniae epidemiology varied by hospital, characterised by clonal diversity; however, in 2022, CG258-tonB79 drove the epidemiology in both hospitals. Conclusions: A more extensive resistance phenotype among CRE was evidenced throughout the COVID-19 pandemic, driven by carbapenemase-producing K. pneumoniae. NDM-5 and KPC-2 were the main carbapenemases identified. A temporal shift in carbapenemase prevalence was observed in each hospital, converging in similar frequencies of KPC and NDM by 2022 across both centres. This scenario was driven by the active dissemination of K. pneumoniae ST258.