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• W3137588305 abstract "Abstract Background Triple-action diazabicyclooctanes, e.g. zidebactam, combine β-lactamase inhibition, antibacterial activity, and ‘enhancement’ of PBP3-targeted β-lactams. Objectives To examine the activity of cefepime/zidebactam against consecutive ‘problem’ Gram-negative bacteria referred to the UK national reference laboratory. Methods MICs were determined by BSAC agar dilution for 1632 Enterobacterales, 745 Pseudomonas aeruginosa and 450 other non-fermenters, categorized by carbapenemase detection and interpretive reading. Results Universal susceptibility to cefepime/zidebactam 8 + 8 mg/L was seen for otherwise multidrug-resistant Enterobacterales with AmpC, extended-spectrum, K1, KPC and OXA-48-like β-lactamases, or with impermeability and ‘unassigned’ mechanisms. Unlike ceftazidime/avibactam and all other comparators, cefepime/zidebactam 8 + 8 mg/L also inhibited most (190/210, 90.5%) Enterobacterales with MBLs. Resistance in the remaining minority of MBL producers, and in 13/24 with both NDM MBLs and OXA-48-like enzymes, was associated with Klebsiella pneumoniae ST14. For Pseudomonas aeruginosa, MICs of cefepime/zidebactam rose with efflux grade, but exceeded 8 + 8 mg/L for only 11/85 isolates even in the highly-raised efflux group. Among 103 P. aeruginosa with ESBLs or MBLs, 97 (94.5%) were inhibited by cefepime/zidebactam 8 + 8 mg/L whereas fewer than 15% were susceptible to any comparator. MICs for Acinetobacter baumannii with acquired OXA carbapenemases clustered around 8 + 8 to 32 + 32 mg/L, with higher values for MBL producers. A strong enhancer effect augmented activity against many isolates that were highly resistant to cefepime and zidebactam alone and which had mechanisms not inhibited by zidebactam. Conclusions Assuming successful clinical trials, cefepime/zidebactam has scope to widely overcome critical resistances in both Enterobacterales and non-fermenters." @default.
• W3137588305 created "2021-03-29" @default.
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• W3137588305 date "2021-03-24" @default.
• W3137588305 modified "2023-10-01" @default.
• W3137588305 title "Activity of cefepime/zidebactam (WCK 5222) against ‘problem’ antibiotic-resistant Gram-negative bacteria sent to a national reference laboratory" @default.
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• W3137588305 doi "https://doi.org/10.1093/jac/dkab067" @default.
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