Activity of novel antibiotics against dual metallo-Beta-lactamase producing <i>Enterobacter hormaechei</i> clinical isolates
Journal
JAC-Antimicrobial Resistance
ISSN
2632-1823
Date Issued
2026-01-07
Author(s)
LORENA DIAZ BAYO
Jose R W Martínez
Nicolas Canales
Yehudit Bergman
Patricia García
Pranita D Tamma
Type
journal-article
Abstract
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Metallo-β-lactamase (MBL)-producing carbapenemase-resistant Enterobacterales infections are associated with significant mortality. Several β-lactam/β-lactamase inhibitor combinations (BL/BLI) with promising activity against MBLs are in the pipeline.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Objective</jats:title>
<jats:p>To investigate the in vitro activity of upcoming BL/BLI agents against Enterobacter hormaechei clinical isolates co-producing NDM and VIM enzymes.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Eleven E. hormaechei isolates co-harbouring blaNDM-7 and blaVIM-1 were identified from 10 patients admitted to a tertiary hospital in Santiago, Chile, between July 2022 and July 2023. Reference broth microdilution (BMD) panels were developed to determine minimum inhibitory concentrations (MICs) to aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, cefiderocol and cefiderocol/xeruborbactam. Cefiderocol population analysis profile–area under the curve (PAP–AUC) was performed in strains exhibiting cefiderocol susceptibility to assess for cefiderocol heteroresistance. Long-read sequencing, using the Oxford Nanopore Technologies platform, was conducted on all isolates to characterize the genomic background of blaNDM-7 and blaVIM-1.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>Among the 11 E. hormaechei isolates assemblies revealed blaNDM-7 and blaVIM-1 were located on separate plasmids. All isolates were susceptible to aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. Cefiderocol susceptibility was variable; the addition of xeruborbactam restored susceptibility.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Our findings indicate that E. hormaechei clinical isolates co-producing NDM and VIM metallo-carbapenemases exhibited susceptibility to all tested novel BL/BLIs, including aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. The combination of cefiderocol and xeruborbactam restored the activity of cefiderocol.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>Metallo-β-lactamase (MBL)-producing carbapenemase-resistant Enterobacterales infections are associated with significant mortality. Several β-lactam/β-lactamase inhibitor combinations (BL/BLI) with promising activity against MBLs are in the pipeline.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Objective</jats:title>
<jats:p>To investigate the in vitro activity of upcoming BL/BLI agents against Enterobacter hormaechei clinical isolates co-producing NDM and VIM enzymes.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods</jats:title>
<jats:p>Eleven E. hormaechei isolates co-harbouring blaNDM-7 and blaVIM-1 were identified from 10 patients admitted to a tertiary hospital in Santiago, Chile, between July 2022 and July 2023. Reference broth microdilution (BMD) panels were developed to determine minimum inhibitory concentrations (MICs) to aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, cefiderocol and cefiderocol/xeruborbactam. Cefiderocol population analysis profile–area under the curve (PAP–AUC) was performed in strains exhibiting cefiderocol susceptibility to assess for cefiderocol heteroresistance. Long-read sequencing, using the Oxford Nanopore Technologies platform, was conducted on all isolates to characterize the genomic background of blaNDM-7 and blaVIM-1.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>Among the 11 E. hormaechei isolates assemblies revealed blaNDM-7 and blaVIM-1 were located on separate plasmids. All isolates were susceptible to aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. Cefiderocol susceptibility was variable; the addition of xeruborbactam restored susceptibility.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Our findings indicate that E. hormaechei clinical isolates co-producing NDM and VIM metallo-carbapenemases exhibited susceptibility to all tested novel BL/BLIs, including aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. The combination of cefiderocol and xeruborbactam restored the activity of cefiderocol.</jats:p>
</jats:sec>