Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales, Pseudomonas aeruginosa , and Acinetobacter baumannii
Year: 2026
Type: article
Abstract: ABSTRACT Detection of GES-type carbapenemases remains challenging because of their low prevalence and frequently weak hydrolytic activity against carbapenems. Carbapenem inactivation method (CIM)-based assays are widely used as phenotypic screening tools for carbapenemase detection; however, their performance in large collections of GES producers has not been systematically evaluated. We assessed the performance of CIM, modified CIM (mCIM), and CIM-Tris in a diverse collection of GES-producing clinical isolates, including 110 Enterobacterales and 108 Pseudomonas aeruginosa, recovered from Spanish hospitals (2010–2024), and 10 Acinetobacter baumannii isolates, mostly obtained from a hospital in Egypt. Whole-genome sequencing was carried out for species confirmation and resistome analysis. Meropenem MICs were determined by broth microdilution. Overall, 92.1% of isolates were GES-carbapenemase producers (CP), whereas 7.9% expressed GES-type extended-spectrum β-lactamases (ESBLs). In Enterobacterales (predominantly carrying bla GES-6 ), mCIM improved sensitivity compared with CIM (63.6% vs 40.0%), although many isolates remained undetected due to low meropenem MICs (MIC 50 , 0.5 µg/mL). In CP- P. aeruginosa (mainly bla GES-5 ), CIM, mCIM, and CIM-Tris showed sensitivities of 89.1%, 94.6%, and 100%, respectively; however, CIM-Tris yielded false-positive results in 50% of non-CP isolates (mostly bla GES-1 producers). Meropenem MICs in P. aeruginosa were higher (MIC 50 , >32 µg/mL). In A. baumannii , CIM-Tris improved sensitivity compared with CIM (100% vs 25.0%). These findings indicate that CIM-based methods can detect GES-type carbapenemases, but performance varies according to bacterial species and GES variant, and reduced specificity may occur in isolates producing GES-type ESBLs. Complementary molecular testing may therefore be necessary to ensure accurate detection of GES-type carbapenemases in routine clinical laboratories. IMPORTANCE GES-type carbapenemases represent an important but underrecognized diagnostic challenge due to their low global prevalence, heterogeneous hydrolytic activity, and the limited performance data available for routine phenotypic detection methods. Although CIM-based assays are widely implemented in clinical microbiology laboratories for carbapenemase screening, their performance against GES-producing organisms has not been comprehensively evaluated across different bacterial genera and GES variants. In this study, we evaluated the performance of CIM, modified CIM (mCIM), and CIM-Tris in a large multicenter collection of well-characterized GES-producing clinical isolates, including Enterobacterales, Pseudomonas aeruginosa , and Acinetobacter baumannii . Our findings demonstrate substantial variability in assay performance according to bacterial species and GES variant. Notably, mCIM improved sensitivity among Enterobacterales with low meropenem MICs, whereas CIM-Tris achieved excellent sensitivity in P. aeruginosa and A. baumannii but at the expense of reduced specificity in isolates producing GES-type ESBLs. To the best of our knowledge, this is the first study directly comparing multiple CIM-based approaches in such a large and taxonomically diverse collection of GES-producing isolates.
Source: Journal of Clinical Microbiology
DOI: 10.1128/jcm.00737-26
Authors: Samuel García-García, Jorge Rodríguez-Grande, María Siller-Ruíz, Cristina Arjona-Torres, Esther Viedma, María Díez-Aguilar, Marta Hernández-García, Javier Fernández-Domínguez, Emilia Cercenado, Fernando Lázaro-Perona, Jesús Oteo-Iglesias, Patricia Ruiz-Garbajosa, Rafael Cantón, Nuria Valcárcel-Fraile, Lucía Gallego, María Pía Roiz-Mesones, Jorge Calvo-Montes, Luis Martínez-Martínez, Alain Ocampo-Sosa, Sergio García-Fernández, on behalf of the GEMARA-GESPABE Study Group
Institutions: Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Instituto Maimónides de Investigación Biomédica de Córdoba, Research Institute Hospital 12 de Octubre, Hospital Universitario 12 De Octubre, Hospital Universitario de La Princesa, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Hospital Universitario Central de Asturias, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Hospital Universitario La Paz, Centro Nacional de Microbiologia, University of the Basque Country, Hospital Universitario Reina Sofía, University of Córdoba, Universidad de Cantabria
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7203914378