Activity of BAL30072 alone or combined with  β-lactamase inhibitors or with meropenem against carbapenem-resistant Enterobacteriaceae and non-fermenters

Mushtaq, Shazad, Woodford, Neil, Hope, Russell, Adkin, Rachael and Livermore, David M. ORCID: https://orcid.org/0000-0002-9856-3703 (2013) Activity of BAL30072 alone or combined with  β-lactamase inhibitors or with meropenem against carbapenem-resistant Enterobacteriaceae and non-fermenters. Journal of Antimicrobial Chemotherapy, 68 (7). pp. 1601-1608. ISSN 0305-7453

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Abstract

Objectives: We investigated the activity of BAL30072, a dihydroxypyridone monosulfactam, against carbapenem-resistant Enterobacteriaceae and non-fermenters (i) alone, (ii) combined with BAL29880 (to inhibit AmpC) and/or clavulanate [to inhibit extended-spectrum ß-lactamases (ESBLs)] and (iii) combined 1:1 with meropenem. Methods: Isolates were from multiple UK hospitals. MICs were determined by CLSI agar dilution. Carbapenemases were identified by PCR and sequencing. Results: BAL30072 inhibited 69% of the carbapenem-resistant Enterobacteriaceae at ≤4 mg/L, including 60%–87% with OXA-48, IMP, NDM and VIM enzymes or combinations of impermeability with AmpC or ESBL, and 40% with KPC enzymes. The proportions susceptible exceeded 90% for BAL30072 + BAL29880 + clavulanate, except for isolates with KPC carbapenemases, where members of the international sequence type (ST) 258 Klebsiella pneumoniae clone remained resistant. At 4 mg/L, BAL30072 was active against all OprD-deficient Pseudomonas aeruginosa, against 8/12 with efflux-type β-lactam resistance and 19/25 with metallo-carbapenemases; these proportions were little increased if inhibitors were added. Most Acinetobacter baumannii with OXA or NDM carbapenemases were susceptible to BAL30072 alone at ≤4 mg/L, but those with OXA-58 were resistant, probably for reasons other than their β-lactamase. Addition of meropenem to BAL30072 increased activity against some individual isolates, but with little clear relationship to the resistance mechanism, except for consistent potentiation against OprD-deficient P. aeruginosa. Conclusions: BAL30072 had good activity against many diverse carbapenem resistance types. Adding clavulanate and/or BAL29880 extended activity against carbapenem-resistant Enterobacteriaceae, but not non-fermenters. Adding meropenem resulted in small increases in activity against individual isolates. Resistance remained common in the K. pneumoniae ST258 KPC clone, even with both inhibitors or meropenem added.

Item Type:	Article
Uncontrolled Keywords:	oxa carbapenemases,kpc carbapenemases,ndm carbapenemases,vim carbapenemases,monosulfactam
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023)
Depositing User:	Pure Connector
Date Deposited:	01 Oct 2013 00:56
Last Modified:	11 Jan 2024 01:26
URI:	https://ueaeprints.uea.ac.uk/id/eprint/43481
DOI:	10.1093/jac/dkt050

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