title: Spanish multicenter study of the epidemiology and mechanisms of amoxicillin-clavulanate resistance in Escherichia coli.
abstract: We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavulanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC ≥ 32/16 μg/ml) were collected at each of the seven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperproduction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC (18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30 (28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79 (2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88 [ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance.
authors.affiliation: Laboratorio de Antibióticos, Bacteriología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ortega
authors.forename: Jesús
authors.initials: J
authors.lastname: Oteo
authors.forename: Maitane
authors.initials: M
authors.lastname: Aranzamendi-Zaldumbide
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Bartolomé
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
authors.forename: Emilia
authors.initials: E
authors.lastname: Cercenado
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Conejo
authors.forename: Juan José
authors.initials: JJ
authors.lastname: González-López
authors.forename: Mercedes
authors.initials: M
authors.lastname: Marín
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Martínez
authors.forename: María
authors.initials: M
authors.lastname: Merino
authors.forename: Ferran
authors.initials: F
authors.lastname: Navarro
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual
authors.forename: Alba
authors.initials: A
authors.lastname: Rivera
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez-Baño
authors.forename: Irene
authors.initials: I
authors.lastname: Weber
authors.forename: Belén
authors.initials: B
authors.lastname: Aracil
authors.forename: José
authors.initials: J
authors.lastname: Campos
mesh_terms: D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000453:epidemiology* / Q000382:microbiology*; D017720:Molecular Epidemiology; D011446:Prospective Studies; D013030:Spain / Q000453:epidemiology
chemical_list: D019980:Amoxicillin-Potassium Clavulanate Combination