title: β-lactamases produced by amoxicillin-clavulanate-resistant enterobacteria isolated in Buenos Aires, Argentina: a new blaTEM gene.
abstract: Resistance to β-lactam/β-lactamase inhibitors in enterobacteria is a growing problem that has not been intensively studied in Argentina. In the present work, 54/843 enterobacteria collected in a teaching hospital of Buenos Aires city were ampicillin-sulbactam-resistant isolates remaining susceptible to second- and third-generation cephalosporins. The enzymatic mechanisms present in the isolates, which were also amoxicillin-clavulanic acid (AMC)-resistant (18/54) were herein analyzed. Sequencing revealed two different variants of blaTEM-1, being blaTEM-1b the most frequently detected allelle (10 Escherichia coli, 3 Klebsiella pneumoniae, 2 Proteus mirabilis and 1 Raoultella terrigena) followed by blaTEM-1a (1 K. pneumoniae). Amoxicillin-clavulanate resistance seems to be mainly associated with TEM-1 overproduction (mostly in E. coli) or co-expressed with OXA-2-like and/or SHV β-lactamases (K. pneumoniae and P. mirabilis). A new blaTEM variant (TEM-163) was described in an E. coli strain having an AMC MIC value of 16/8μg/ml. TEM-163 contains Arg275Gln and His289Leu amino acid substitutions. On the basis of the high specific activity and low IC50 for clavulanic acid observed, the resistance pattern seems to be due to overproduction of the new variant of broad spectrum β-lactamase rather than to an inhibitor-resistant TEM (IRT)-like behavior.
authors.affiliation: Facultad de Farmacia y Bioquímica, UBA, Ciudad Autónoma de Buenos Aires, Argentina; Facultad de Bioquímica y Ciencias Biológicas, UNL, Santa Fe, Argentina. Electronic address: jdiconza@fbcb.unl.edu.ar.
authors.forename: José A
authors.initials: JA
authors.lastname: Di Conza
authors.affiliation: Facultad de Farmacia y Bioquímica, UBA, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Badaracco
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", CSIC - UAM, Cantoblanco, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ayala
authors.affiliation: Facultad de Farmacia y Bioquímica, UBA, Ciudad Autónoma de Buenos Aires, Argentina; Hospital de Clínicas de la UBA "José de San Martín", Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Rodríguez
authors.affiliation: Facultad de Farmacia y Bioquímica, UBA, Ciudad Autónoma de Buenos Aires, Argentina; Hospital de Clínicas de la UBA "José de San Martín", Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Angela
authors.initials: A
authors.lastname: Famiglietti
authors.affiliation: Facultad de Farmacia y Bioquímica, UBA, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Gabriel O
authors.initials: GO
authors.lastname: Gutkind
mesh_terms: D019943:Amino Acid Substitution; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000494:pharmacology*; D001118:Argentina / Q000453:epidemiology; D001483:Base Sequence; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology; D004269:DNA, Bacterial / Q000235:genetics; D052978:Disk Diffusion Antimicrobial Tests; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology / Q000382:microbiology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D029968:Escherichia coli Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D005798:Genes, Bacterial; D006784:Hospitals, Teaching; D006786:Hospitals, Urban; D006801:Humans; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid; D013379:Substrate Specificity; D001618:beta-Lactamases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D019980:Amoxicillin-Potassium Clavulanate Combination; D001618:beta-Lactamases
keywords: Amoxicillin-clavulanate resistance; Enterobacteria; Hiperproducción de TEM-1; Resistencia a amoxicilina-ácido clavulánico; TEM-1 overproduction; TEM-163