2. Academic Validation
  3. Comparative activity of established versus new-generation β-lactams against AmpC-hyperproducing clinical isolates of Enterobacter cloacae complex and Klebsiella aerogenes: a multicentre study

Comparative activity of established versus new-generation β-lactams against AmpC-hyperproducing clinical isolates of Enterobacter cloacae complex and Klebsiella aerogenes: a multicentre study

  • J Antimicrob Chemother. 2026 Feb 2;81(3):dkag034. doi: 10.1093/jac/dkag034.
Ángel Rodríguez-Villodres 1 2 3,  Jesús Rodríguez-Lozano 3 4,  Alba Mir-Cros 3 5,  Natalia Chueca 3 6,  Marta Rodríguez-Rodríguez 1 2,  Nuria Fraile-Valcárcel 3 4,  Guillem Puigsech-Boixeda 3 5,  Carmen Fernández-Bermudo 1 2,  Dolors Rodríguez-Pardo 3 7,  Cristina Arjona-Torres 8,  Javier E Cañada-García 3 9,  Silvia García-Cobos 3 9,  Irene Gracia-Ahufinger 3 8 10 11,  Cristina Ortega-Portas 12,  Jaime Esteban 3 12,  Sara M Soto 3 13 14,  José Miguel Cisneros 1 2 3 15,  José Antonio Lepe 1 2 3 16
Affiliations

Affiliations

  • 1 Clinical Unit of Infectious Diseases, Microbiology and Parasitology, University Hospital Virgen del Rocío, Av. Manuel Siurot s/n, Seville 41013, Spain.
  • 2 Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain.
  • 3 Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
  • 4 Microbiology Service, University Hospital Marqués de Valdecilla-IDIVAL, Cantabria, Spain.
  • 5 Microbiology Research Group, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain.
  • 6 Microbiology Service, University Hospital Clinico San Cecilio, Granada, Spain.
  • 7 Infectious Diseases Service, University Hospital Vall d'Hebron, Barcelona, Spain.
  • 8 Maimonides Biomedical Research Institute of Cordoba, Reina Sofía University Hospital, University of Cordoba (IMIBIC/HURS/UCO), Cordoba, Spain.
  • 9 Laboratorios de Referencia e Investigación en Resistencia a Antibióticos e Infecciones Relacionadas con la Asistencia Sanitaria, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
  • 10 Microbiology Unit, University Hospital Reina Sofía, Córdoba, Spain.
  • 11 Department of Agricultural Chemistry, Soil Science and Microbiology, University of Córdoba, Córdoba, Spain.
  • 12 Department of Clinical Microbiology, IIS-Fundación Jiménez Díaz, Madrid, UAM, Madrid, Spain.
  • 13 Barcelona Institute for Global Heart (ISGlobal), HBarcelona, Spain.
  • 14 Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
  • 15 Faculty of Medicine, University of Seville, Seville, Spain.
  • 16 Department of Microbiology, University of Seville, Seville, Spain.
PMID: 41648989 DOI: 10.1093/jac/dkag034
Abstract

Background: Antimicrobial resistance among Enterobacter cloacae complex and Klebsiella aerogenes is a growing clinical challenge, often driven by AmpC β-lactamase hyperproduction. This phenotype limits therapeutic options to cefepime or carbapenems.

Objectives: To assess the in vitro activity of conventional β-lactams, such as cefepime, piperacillin/tazobactam or carbapenems, and new-generation agents, including ceftazidime/avibactam, cefepime/taniborbactam, imipenem/relebactam, meropenem/vaborbactam, and cefiderocol, against AmpC-hyperproducing E. cloacae complex and K. aerogenes.

Methods: A total of 314 clinical isolates (200 E. cloacae complex and 114 K. aerogenes) recovered between March and December 2024, from eight Spanish centres were tested by broth microdilution (EUCAST). AmpC hyperproduction was confirmed phenotypically and carbapenemase was screened phenotypically/molecularly. WGS was performed for (i) 84 E. cloacae complex isolates, and (ii) six isolates with reduced susceptibility to at least one novel agent.

Results: High resistance rates were observed for piperacillin/tazobactam (up to 82.4%) and cefepime (up to 20.5%), whereas carbapenems showed variable activity. New-generation agents exhibited excellent activity, with susceptibility rates ≥99% in both species. Resistance to at least one new agent was found in only six isolates. In the WGS-analysed E. cloacae complex subset, Enterobacter hormaechei predominated (75%) with high STs and blaACT allele diversity. In the six reduced-susceptibility isolates, no carbapenemase or explanatory acquired β-lactamase was found.

Conclusions: Our findings underscore the need to take this phenotype into account in clinical practice and confirm the limited activity of conventional β-lactams against AmpC-hyperproducing E. cloacae complex and K. aerogenes, and support the use of newer agents as effective alternatives.

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