Ambler class C-type β-lactamases and porin alterations in Enterobacter cloacae complex and Klebsiella aerogenes in the Netherlands, 2012–2023
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<sub>ACT-28</sub>, bla<sub>ACT-52,</sub> bla<sub>MIR-3</sub>, bla<sub>MIR-11</sub> 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<sub>ACT-28</sub> 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.
Authors
- Gert-Jan Godeke
- Fabian Landman (ORCID: https://orcid.org/0000-0001-6543-836X)
- Herman F. Wunderink
- Cornelia C. H. Wielders
- Elke van Gorp
- Simon Lansu
- Jeroen Bos (ORCID: https://orcid.org/0009-0001-3278-2591)
- Angela de Haan
- Maurits P. A. van Meer
- Maureen Ouw
- Antoni P. A. Hendrickx
- B. M. W. Diederen
- A. E. Muller
- E. I. G. B. de Brauwer
- J. J. J. M. Stohr
- D. C. Melles
- W. Ang
- S. P. van Mens
- B. Zwart
- A. Ott
- J. W. T. Cohen Stuart
- M. den Reijer
- S. J. Vainio
- J. C. Sinnige
- H. Berkhout
- D. W. van Dam
- F. Koene
- A. Jansz
- B. Maraha
- A. J. van Griethuysen
- L. G. M. Bode
- J. de Vries
- E. de Jong
- M. van Rijn
- M. J. C. A. van Trijp
- E. Kolwijck
- J. da Silva
- M. P. M. van der Linden
- E. Heikens
- K. Waar
- S. B. Debast
- R. Steingrover
- C. Oliveira dos Santos
- M. Wong
- Sandra Witteveen
- A. Troelstra
- A. P. van Dam
- N. Al Naiemi
- T. Schulin
- M. P. A. van Meer
- Wil van der Zwet
- W. van den Bijllaardt
- E. van der Vorm
- A. L. E. van Arkel
- E. Bathoorn
- M. de Graaf
- I. Maat
- J. W. Dorigo-Zetsma
- P. Gruteke
- S. Paltansing
- J. R. Lo Ten Foe
- K. van Dijk
- Daan W. Notermans
- A. L. M. Vlek
- S. Dinant
- R. van Mansfeld
- M. A. Leversteijn-van Hall
Institutions
- Maastricht University Medical Centre (NL)
- University Medical Center Utrecht (NL)
- Maastricht University (NL)
- National Institute for Public Health and the Environment (NL)
- Rijnstate Hospital (NL)
Publication Details
- Journal
- BMC Microbiology
- Published
- 2026-01-30
- DOI
- https://doi.org/10.1186/s12866-026-04741-1
- Citations
- 1
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 21.79