NXL104 combinations versus Enterobacteriaceae with CTX-M extended-spectrum β-lactamases and carbapenemases

Livermore, David M. ORCID: https://orcid.org/0000-0002-9856-3703, Mushtaq, Shazad, Warner, Marina, Miossec, Christine and Woodford, Neil (2008) NXL104 combinations versus Enterobacteriaceae with CTX-M extended-spectrum β-lactamases and carbapenemases. Journal of Antimicrobial Chemotherapy, 62 (5). pp. 1053-1056. ISSN 0305-7453

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Abstract

Background The ß-lactamase landscape is changing radically, with CTX-M types now the most prevalent extended-spectrum ß-lactamases (ESBLs) worldwide, except maybe in the USA. In addition, there are growing numbers of Enterobacteriaceae with KPC and metallo-carbapenemases. We examined whether combinations of oxyimino-cephalosporins with NXL104, a novel non-ß-lactam ß-lactamase inhibitor, overcame these resistances. Methods NXL104 was tested at 4 mg/L in combination with cefotaxime and ceftazidime versus: (i) Escherichia coli transconjugants and wild-type Enterobacteriaceae with CTX-M ESBLs; (ii) Enterobacteriaceae with ertapenem resistance contingent on combinations of impermeability and ESBLs or AmpC; and (iii) Enterobacteriaceae with KPC, SME, metallo- or OXA-48 carbapenemases. Results MICs of cefotaxime + NXL104 were =1 mg/L for most Enterobacteriaceae with CTX-M, KPC or OXA-48 enzymes and were =2 mg/L for those that also had ertapenem resistance contingent on combinations of ß-lactamase and impermeability. MICs of the ceftazidime + NXL104 combination were =4 mg/L, except for a single Enterobacter aerogenes with KPC and AmpC enzymes together with porin loss, which required an MIC of 32 mg/L. The major gap was that NXL104 could not potentiate cephalosporins against Enterobacteriaceae with IMP or VIM metallo-enzymes. Conclusions Oxyimino-cephalosporin + NXL104 combinations have potential against strains with the prevalent ESBLs and non-metallo-carbapenemases.

Item Type:	Article
Uncontrolled Keywords:	anti-bacterial agents,cefotaxime,ceftazidime,enterobacteriaceae,enzyme inhibitors,microbial sensitivity tests,molecular structure,beta-lactamases,beta-lactams
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023) Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health
Depositing User:	Rhiannon Harvey
Date Deposited:	07 Jul 2011 11:09
Last Modified:	11 Jan 2024 01:22
URI:	https://ueaeprints.uea.ac.uk/id/eprint/33443
DOI:	10.1093/jac/dkn320

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