Ambler class C-type β-lactamases and porin alterations in Enterobacter cloacae complex and Klebsiella aerogenes in the Netherlands, 2012-2023
van Gorp, Elke Lansu, Simon Wielders, Cornelia CH de Haan, Angela Godeke, Gert-Jan Witteveen, Sandra Bos, Jeroen Landman, Fabian Ouw, Maureen Wunderink, Herman F
van Gorp, Elke
Lansu, Simon
Wielders, Cornelia CH
de Haan, Angela
Godeke, Gert-Jan
Witteveen, Sandra
Bos, Jeroen
Landman, Fabian
Ouw, Maureen
Wunderink, Herman F
Series / Report no.
Open Access
Type
Journal Article
Article
Article
Language
en
Date of publication
2026-01-30
Year of publication
Research Projects
Organizational Units
Journal Issue
Title
Ambler class C-type β-lactamases and porin alterations in Enterobacter cloacae complex and Klebsiella aerogenes in the Netherlands, 2012-2023
Translated Title
Published in
BMC Microbiol 2026; 26(1):192
Abstract
We investigated the genomic epidemiology of Ambler class C (AmpC-type) β-lactamases in Enterobacter cloacae complex and Klebsiella aerogenes in the national carbapenemase-producing Enterobacterales (CPE) surveillance of the Netherlands between 2012 and 2023. A total of 399 E. cloacae complex and K. aerogenes isolates from 399 patients were analyzed using whole-genome sequencing to assess genetic relatedness, resistance genes, porin, and AmpC-regulatory gene profiles, plasmid replicons, and the genomic location of AmpC-genes, respectively. Of the 399 patients, 217 were male (54%), and the median age was 67 years. Carbapenemase production was assessed using the carbapenem inactivation method (CIM) and CarbaNP-test. A considerable proportion of E. cloacae complex (32%) and K. aerogenes (52%) isolates were CIM-positive in the absence of detectable carbapenemase genes (IMP, KPC, NDM, OXA-48-like, VIM) by the CarbaPCR, a phenotype termed CIM + Carba-. These isolates were mostly (81.9%) susceptible (EUCAST ≤ 2mg/L) to meropenem. The majority of CIM + Carba + isolates with major carbapenemase genes were gained from pre-emptive screening, while CIM + Carba- isolates were mainly taken for diagnostic purposes. Genomic analysis identified 18 genogroups, with E. kobei, E. roggenkampii, E. ludwigii, and K. aerogenes showing the CIM + Carba- phenotype, were mostly lacking porins and AmpC regulators, and correlated with chromosome-encoded AmpC-type β-lactamases like bla, bla bla, bla or ampC of which the majority (63%) yielded a positive CarbaNP-test. These CIM + Carba- isolates carried only few plasmids, and there was limited evidence of nosocomial spread. CIM + Carba- E. kobei carrying bla overproduced ACT-28 protein in the CIM. Overall, the Enterobacter and K. aerogenes population in the Netherlands is genetically diverse, with most isolates carrying species-specific AmpC-type β-lactamases. Isolates with low MIC for meropenem that lack porins and major carbapenemases represent a low-risk for public health.