MIC of amoxicillin/clavulanate according to CLSI and EUCAST: Discrepancies and clinical impact in patients with bloodstream infections due to Enterobacteriaceae

Mercedes Delgado-Valverde, Adoración Valiente-Mendez, Eva Torres, Benito Almirante, Silvia Gómez-Zorrilla, Nuria Borrell, Ana Isabel Aller-García, Mercedes Gurgui, Manel Almela, Mercedes Sanz, Germán Bou, Luis Martínez-Martínez, Rafael Cantón, Jose Antonio Lepe, Manuel Causse, Belén Gutiérrez-Gutiérrez, Álvaro Pascual, Jesús Rodríguez-Baño, Marina de Cueto, Ana María Planes-ReigFe Tubau-Quintano, Carmen Peña, Carlos Ruíz de Alegría, M. Isabel Morosini, Adriana Shan, José Miguel Cisneros, J. Enrique Corzo, Núria Prim, María Elvira Galán, Lara García-Álvarez, Irene Gracia-Ahufinger, Julia Guzmán-Puche, Julián Torre-Cisneros

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15 Citations (Scopus)


© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Objectives: To compare results of amoxicillin/clavulanate susceptibility testing using CLSI and EUCAST methodologies and to evaluate their impact on outcome in patients with bacteraemia caused by Enterobacteriaceae. Patients and methods: A prospective observational cohort study was conducted in 13 Spanish hospitals. Patients with bacteraemia due to Enterobacteriaceae who received empirical intravenous amoxicillin/clavulanate treatment for at least 48h were included. MICs were determined following CLSI and EUCAST recommendations. Outcome variables were: failure at the end of treatment with amoxicillin/clavulanate (FEAMC); failure at day 21; and 30 day mortality. Classification and regression tree (CART) analysis and logistic regression were performed. Results: Overall, 264 episodes were included; the urinary tract was the most common source (64.7%) and Escherichia coli themost frequent pathogen (76.5%). Fifty-two isolates (19.7%) showed resistance according to CLSI and 141 (53.4%) according to EUCAST. The kappa index for the concordance between the results of both committees was only 0.24. EUCAST-derived, but not CLSI-derived, MICs were associated with failure when considered as continuous variables. CART analysis suggested a 'resistance' breakpoint of > 8/4mg/L for CLSI-derived MICs; it predicted FEAMC in adjusted analysis (OR=1.96; 95% CI: 0.98-3.90). Isolates with EUCAST-derived MICs > 16/2 mg/L independently predicted FEAMC (OR=2.10; 95%CI: 1.05-4.21) and failure at day 21 (OR=3.01; 95%CI: 0.93-9.67).MICs.32/2mg/Lwere only predictive of failure among patientswith bacteraemia from urinary or biliary tract sources. Conclusions: CLSI and EUCAST methodologies showed low agreement for determining the MIC of amoxicillin/clavulanate. EUCAST-derived MICs seemed more predictive of failure than CLSI-derived ones. EUCAST-derived MICs > 16/2 mg/L were independently associated with therapeutic failure.
Original languageEnglish
Pages (from-to)1478-1487
JournalJournal of Antimicrobial Chemotherapy
Issue number5
Publication statusPublished - 1 Jan 2017


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