title: MIC of amoxicillin/clavulanate according to CLSI and EUCAST: discrepancies and clinical impact in patients with bloodstream infections due to Enterobacteriaceae.
abstract: 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.
  
  
  
  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 48 h 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.
  
  
  
  Overall, 264 episodes were included; the urinary tract was the most common source (64.7%) and Escherichia coli the most 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 > 8/4 mg/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 >32/2 mg/L were only predictive of failure among patients with bacteraemia from urinary or biliary tract sources.
  
  
  
  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.
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío-IBiS, Seville, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado-Valverde
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío-IBiS, Seville, Spain.
authors.forename: Adoración
authors.initials: A
authors.lastname: Valiente-Mendez
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío-IBiS, Seville, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Torres
authors.affiliation: Departamento de Enfermedades Infecciosas, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Benito
authors.initials: B
authors.lastname: Almirante
authors.affiliation: Servicio de Enfermedades Infecciosas, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gómez-Zorrilla
authors.affiliation: Servicio de Microbiología, Hospital Son Espases, Palma de Mallorca, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Borrell
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Seville, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Aller-García
authors.affiliation: Servicio de Enfermedades Infecciosas, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.|Facultad de Medicina, Universitat Autònomade Barcelona, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Gurgui
authors.affiliation: Servicio de Microbiología, Hospital Clínic, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Almela
authors.affiliation: Departamento de Enfermedades Infecciosas, Hospital San Pedro-CIBIR, Logroño, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sanz
authors.affiliation: Servicio de Microbiología, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
authors.affiliation: Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Santander, Spain.|Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Martínez
authors.affiliation: Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cantón
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío-IBiS, Seville, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Antonio Lepe
authors.affiliation: Unidad de Gestión Clínica de Microbiología, Hospital Universitario Reina Sofía-Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Causse
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío-IBiS, Seville, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Gutiérrez-Gutiérrez
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío-IBiS, Seville, Spain.|Departamento de Microbiología, Universidad de Sevilla, Seville, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Pascual
authors.affiliation: Unidad Clínica Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío-IBiS, Seville, Spain.|Departamento de Medicina, Universidad de Sevilla, Seville, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez-Baño
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D004755:Enterobacteriaceae / Q000187:drug effects*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D019980:Amoxicillin-Potassium Clavulanate Combination