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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background/Objectives: Metallo-β-lactamases (MBLs) in Enterobacterales and other Gram-negative organisms pose significant public health threats due to their association with multidrug resistance (MDR). Although aztreonam (AZT) can target MBL-producing organisms, its efficacy is compromised in organisms expressing additional β-lactamases that inactivate it. Combining AZT with the β-lactamase inhibitor avibactam (AVI) may restore its activity against MBL-producing isolates. Methods: AZT-AVI, along with other clinically relevant antimicrobials, was tested against thirteen MBL-producing clinical isolates of Enterobacterales (nine Klebsiella pneumoniae, three Enterobacter cloacae, and one Providencia stuartii) using whole-genome sequencing (WGS) for genetic characterization. Results: AZT-AVI demonstrated full susceptibility across all isolates, whereas aztreonam alone was ineffective. The newer β-lactam/β-lactamase inhibitor combinations imipenem/relebactam and meropenem/vaborbactam were inactive in 100% and 92.3% of isolates, respectively. WGS-based analysis revealed multiple resistance mechanisms consistent with MDR phenotypes, including high-risk K. pneumoniae clones (ST147 and ST11). Conclusions: AZT-AVI is effective against MDR MBL-producing Enterobacterales, highlighting its therapeutic potential for challenging infections. While WGS does not replace phenotypic testing, it provides valuable insights for antimicrobial stewardship and the monitoring of resistance gene dissemination.

Details

Title
Characterization of Metallo β-Lactamase Producing Enterobacterales Isolates with Susceptibility to the Aztreonam/Avibactam Combination
Author
Posteraro, Brunella 1 ; De Maio, Flavio 2   VIAFID ORCID Logo  ; Spanu, Teresa 2 ; Vidal Pereira, Maria Alejandra 3   VIAFID ORCID Logo  ; Fasano, Francesca Romana 3 ; Sanguinetti, Maurizio 4   VIAFID ORCID Logo 

 Unità Operativa “Medicina di Precisione in Microbiologia Clinica”, Direzione Scientifica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; [email protected]; Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy 
 Dipartimento di Scienze di Laboratorio ed Ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; [email protected] (F.D.M.); [email protected] (T.S.) 
 Medical Affairs, Pfizer Italia, 00188 Rome, Italy; [email protected] (M.A.V.P.); [email protected] (F.R.F.) 
 Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; Dipartimento di Scienze di Laboratorio ed Ematologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; [email protected] (F.D.M.); [email protected] (T.S.) 
First page
1221
Publication year
2024
Publication date
2024
Publisher
MDPI AG
e-ISSN
20796382
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3149503625
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.