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In vitro activity of cefepime/zidebactam (WCK 5222) against Gram-negative bacteria.
- Source :
- Journal of Antimicrobial Chemotherapy (JAC); May2017, Vol. 72 Issue 5, p1373-1385, 13p
- Publication Year :
- 2017
-
Abstract
- <bold>Objectives: </bold>Diazabicyclooctanes (DBOs) inhibit class A, class C and some class D β-lactamases. A few also bind PBP2, conferring direct antibacterial activity and a β-lactamase-independent 'enhancer' effect, potentiating β-lactams targeting PBP3. We tested a novel DBO, zidebactam, combined with cefepime.<bold>Methods: </bold>CLSI agar dilution MICs were determined with cefepime/zidebactam in a chequerboard format. Bactericidal activity was also measured.<bold>Results: </bold>Zidebactam MICs were ≤2 mg/L (mostly 0.12-0.5 mg/L) for most Escherichia coli , Klebsiella , Citrobacter and Enterobacter spp., but were >32 mg/L for Proteeae, most Serratia and a few E. coli , Klebsiella and Enterobacter/Citrobacter . The antibacterial activity of zidebactam dominated chequerboard studies for Enterobacteriaceae, but potentiation of cefepime was apparent for zidebactam-resistant isolates with class A and C enzymes, illustrating β-lactamase inhibition. Overall, cefepime/zidebactam inhibited almost all Enterobacteriaceae with AmpC, ESBL, K1, KPC and OXA-48-like β-lactamases at 1 + 1 mg/L and also 29 of 35 isolates with metallo-carbapenemases, including several resistant to zidebactam alone. Zidebactam MICs for 36 of 50 Pseudomonas aeruginosa were 4-16 mg/L, and the majority of AmpC, metallo-β-lactamase-producing and cystic fibrosis isolates were susceptible to cefepime/zidebactam at 8 + 8 mg/L. Zidebactam MICs for Acinetobacter baumannii and Stenotrophomonas maltophilia were >32 mg/L; potentiation of cefepime was frequent for S. maltophilia , but minimal for A. baumannii . Kill curve results largely supported MICs.<bold>Conclusions: </bold>Zidebactam represents a second triple-action DBO following RG6080, with lower MICs for Enterobacteriaceae and P. aeruginosa . Clinical evaluation of cefepime/zidebactam must critically evaluate the reliance that can be placed on this direct antibacterial activity and on the enhancer effect as well as β-lactamase inhibition. [ABSTRACT FROM AUTHOR]
- Subjects :
- DIAZABICYCLOOCTANE
BETA lactamases
ANTIBACTERIAL agents
LACTAMS
CEFEPIME
GRAM-negative bacteria
THERAPEUTICS
ANTIBIOTICS
CEPHALOSPORINS
ENTEROBACTERIACEAE
ENZYME inhibitors
ESCHERICHIA coli
HYDROCARBONS
KLEBSIELLA
MICROBIAL sensitivity tests
ORGANIC compounds
PIPERIDINE
CITROBACTER
ENTEROBACTERIACEAE diseases
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 03057453
- Volume :
- 72
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Journal of Antimicrobial Chemotherapy (JAC)
- Publication Type :
- Academic Journal
- Accession number :
- 122690339
- Full Text :
- https://doi.org/10.1093/jac/dkw593