title: In vitro antibacterial activity of the ceftazidime-avibactam combination against enterobacteriaceae, including strains with well-characterized β-lactamases.
abstract: The novel β-lactamase inhibitor avibactam is a potent inhibitor of class A, class C, and some class D enzymes. The in vitro antibacterial activity of the ceftazidime-avibactam combination was determined for a collection of Enterobacteriaceae clinical isolates; this collection was enriched for resistant strains, including strains with characterized serine β-lactamases. The inhibitor was added either at fixed weight ratios to ceftazidime or at fixed concentrations, with the latter type of combination consistently resulting in greater potentiation of antibacterial activity. In the presence of 4 μg/ml of avibactam, the ceftazidime MIC50 and MIC90 (0.25 and 2 μg/ml, respectively) were both below the CLSI breakpoint for ceftazidime. Further comparisons with reference antimicrobial agents were performed using this fixed inhibitor concentration. Against most ceftazidime-susceptible and -nonsusceptible isolates, the addition of avibactam resulted in a significant increase in ceftazidime activity, with MICs generally reduced 256-fold for extended-spectrum β-lactamase (ESBL) producers, 8- to 32-fold for CTX-M producers, and >128-fold for KPC producers. Overall, MICs of a ceftazidime-avibactam combination were significantly lower than those of the comparators piperacillin-tazobactam, cefotaxime, ceftriaxone, and cefepime and similar or superior to those of imipenem.
authors.affiliation: Novexel SA, Romainville, France.
authors.forename: Premavathy
authors.initials: P
authors.lastname: Levasseur
authors.affiliation: Novexel SA, Romainville, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Girard
authors.affiliation: Novexel SA, Romainville, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Miossec
authors.affiliation: Novexel SA, Romainville, France.
authors.forename: John
authors.initials: J
authors.lastname: Pace
authors.affiliation: Novexel SA, Romainville, France kenclmn45@gmail.com.
authors.forename: Ken
authors.initials: K
authors.lastname: Coleman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; C543519:avibactam; D002442:Ceftazidime; D001618:beta-Lactamases