| Title: |
Ambler class C-type β-lactamases and porin alterations in Enterobacter cloacae complex and Klebsiella aerogenes in the Netherlands, 2012-2023 |
| Authors: |
van Gorp,Elke; Lansu,Simon; Wielders,Cornelia C H; de Haan,Angela; Godeke,Gert-Jan; Witteveen,Sandra; Bos,Jeroen; Landman,Fabian; Ouw,Maureen; Wunderink, Herman F; van Meer,M P A; van der Zwet,Wil; Notermans,Daan W; Hendrickx, Antoni P A; van Arkel,A L E; Leversteijn-van Hall,M A; van den Bijllaardt,W; van Mansfeld,R; van Dijk,K; Zwart,B; Diederen,B M W; Berkhout,H; Ott,A; Waar,K; Ang,W; da Silva,J; Vlek,A L M; Stohr,J J J M; Bode, L G M; Jansz,A; Paltansing,S; van Griethuysen,A J; Lo Ten Foe,J R; van Trijp,M J C A; Wong,M; Muller,A E; van der Linden,M P M; van Rijn,M; Debast,S B; Kolwijck,E; Al Naiemi,N; Schulin,T; Dinant,S; van Mens,S P; Melles,D C; Stuart,J W T Cohen; Gruteke,P; van Dam,A P; Maat,I; Maraha,B; Sinnige,J C; van der Vorm,E; de Graaf,M; de Jong,E; Vainio,S J; Heikens, E; den Reijer,M; Dorigo-Zetsma,J W; Troelstra, A; Bathoorn,E; de Vries,J; van Dam,D W; de Brauwer,E I G B; Steingrover,R; Koene,F; Oliveira Dos Santos,C; MMB opleiding Arts microbioloog; Infection & Immunity; MMB-mcb; MMB Medische Staf; MMB Infectiepreventie |
| Publication Year: |
2026 |
| Subject Terms: |
Journal Article |
| Description: |
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 blaACT-28, blaACT-52, blaMIR-3, blaMIR-11 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 blaACT-28 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
1471-2180 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/469378 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/469378 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.88DD76E4 |
| Database: |
BASE |