Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Organisms Collected from U.S. Medical Centers in 2012

Abstract

ABSTRACTThe activities of the novel β-lactam–β-lactamase inhibitor combination ceftazidime-avibactam and comparator agents were evaluated against a contemporary collection of clinically significant Gram-negative bacilli. Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits Ambler class A, C, and some D enzymes. A total of 10,928 Gram-negative bacilli—8,640Enterobacteriaceae, 1,967Pseudomonas aeruginosa, and 321Acinetobactersp. isolates—were collected from 73 U.S. hospitals and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories, North Liberty, IA, USA). Ceftazidime was combined with avibactam at a fixed concentration of 4 μg/ml. Overall, 99.8% ofEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. Ceftazidime-avibactam was active against extended-spectrum β-lactamase (ESBL)-phenotypeEscherichia coliandKlebsiella pneumoniae, meropenem-nonsusceptible (MIC ≥ 2 μg/ml)K. pneumoniae, and ceftazidime-nonsusceptibleEnterobacter cloacae. Among ESBL-phenotypeK. pneumoniaestrains, 61.1% were meropenem susceptible and 99.3% were inhibited at a ceftazidime-avibactam MIC of ≤4 μg/ml. AmongP. aeruginosastrains, 96.9% were inhibited at a ceftazidime-avibactam MIC of ≤8 μg/ml, and susceptibility rates for meropenem, ceftazidime, and piperacillin-tazobactam were 82.0, 83.2, and 78.3%, respectively. Ceftazidime-avibactam was the most active compound tested against meropenem-nonsusceptibleP. aeruginosa(MIC50/MIC90, 4/16 μg/ml; 87.3% inhibited at ≤8 μg/ml).Acinetobacterspp. (ceftazidime-avibactam MIC50/MIC90, 16/>32 μg/ml) showed high rates of resistance to most tested agents. In summary, ceftazidime-avibactam demonstrated potent activity against a large collection of contemporary Gram-negative bacilli isolated from patients in U.S. hospitals in 2012, including organisms that are resistant to most currently available agents, such asK. pneumoniaecarbapenemase (KPC)-producingEnterobacteriaceaeand meropenem-nonsusceptibleP. aeruginosa.