Activity of chequerboard combinations of ceftaroline and NXL104 versus -lactamase-producing Enterobacteriaceae

Mushtaq, S., Warner, M., Williams, G., Critchley, I. and Livermore, DM (2010) Activity of chequerboard combinations of ceftaroline and NXL104 versus -lactamase-producing Enterobacteriaceae. Journal of Antimicrobial Chemotherapy, 65 (7). pp. 1428-1432. ISSN 0305-7453

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Abstract

Background Ceftaroline is a novel oxyimino-cephalosporin, strongly active against methicillin-resistant staphylococci and pneumococci. It is active against Enterobacteriaceae too, but is labile to common ß-lactamases, including AmpC and extended-spectrum types. To counteract these enzymes, ceftaroline is also being developed combined with NXL104, a ß-lactamase inhibitor. Methods Chequerboard MIC titrations were performed to determine the NXL104 concentrations needed to protect ceftaroline against ß-lactamase-producing Enterobacteriaceae, most of them with ceftaroline MICs >16 mg/L. Results All of 60 extended-spectrum ß-lactamase (ESBL) producers were susceptible to ceftaroline?+?NXL104, 1?+?1 mg/L, as were 5/5 Klebsiella oxytoca with high-level K1 enzyme. Among 30 Enterobacteriaceae with high-level chromosomal AmpC, 18 were susceptible at 1?+?1 mg/L, 28 at 1?+?4 mg/L and all at 4?+?4 mg/L; among 10 with plasmid AmpC enzymes, nine were susceptible at 1?+?1 mg/L and all at 1?+?4 mg/L. None of 10 isolates with combinations of AmpC or ESBL and impermeability was susceptible at 1?+?1 mg/L, but nine were susceptible at 1?+?4 mg/L and all at 4?+?4 mg/L. Among 12 with KPC carbapenemases, only two were susceptible at 1?+?1 mg/L, compared with 10 at 1?+?4 mg/L and 11 at 4?+?4 mg/L; 8/8 with OXA-48 carbapenemase were susceptible at 1?+?1 mg/L whilst 0/5 with metallo-ß-lactamases were inhibited by ceftaroline?+?NXL104, even at 8?+?4 mg/L. NXL104 potentiated the activity of ceftaroline against many ESBL- and AmpC-negative isolates for which ceftaroline MICs were 1–4 mg/L but not those for which MICs were =0.5 mg/L, probably reflecting the slight lability of this cephalosporin to classical penicillinases, which were present in the former group but not the latter. Conclusions At concentrations of =4 mg/L, NXL104 protected ceftaroline against all relevant ß-lactamases except metalloenzymes.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Rhiannon Harvey
Date Deposited: 05 Jul 2011 10:56
Last Modified: 21 Apr 2020 17:00
URI: https://ueaeprints.uea.ac.uk/id/eprint/33345
DOI: 10.1093/jac/dkq161

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