title: Activity of NXL104 in combination with beta-lactams against genetically characterized Escherichia coli and Klebsiella pneumoniae isolates producing class A extended-spectrum beta-lactamases and class C beta-lactamases.
abstract: The novel non-β-lactam β-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae isolates, 94 AmpC-hyperproducing E. coli isolates, and 8 AmpC/ESBL-coexpressing E. coli isolates. NXL104 restored 100% susceptibility to the partner cephalosporins for all isolates tested. Amdinocillin and meropenem MICs were modestly improved (2 to 32 times lower) by NXL104. These results suggest that NXL104 may be useful in combination with β-lactams for the treatment of infections caused by ESBL- and AmpC-producing Enterobacteriaceae.
authors.affiliation: Saint-Boniface Hospital, Department of Medical Microbiology and Infectious Diseases, Faculty of Medicine, University of Manitoba, L4025-409 Taché Ave., Winnipeg, Manitoba, Canada R2H 2A6. plagacewiens@dsmanitoba.ca
authors.forename: P R S
authors.initials: PR
authors.lastname: Lagacé-Wiens
authors.forename: F
authors.initials: F
authors.lastname: Tailor
authors.forename: P
authors.initials: P
authors.lastname: Simner
authors.forename: M
authors.initials: M
authors.lastname: DeCorby
authors.forename: J A
authors.initials: JA
authors.lastname: Karlowsky
authors.forename: A
authors.initials: A
authors.lastname: Walkty
authors.forename: D J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: G G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D053961:Azabicyclo Compounds / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D053961:Azabicyclo Compounds; D047090:beta-Lactams; C543519:avibactam; D001618:beta-Lactamases