Antimicrobial Activity of Ceftazidime-Avibactam Tested against Multidrug-Resistant Enterobacteriaceae and Pseudomonas aeruginosa Isolates from United States Medical Centers (2013--2016) [PublishAheadOfPrint]

The in vitro activity of ceftazidime-avibactam and many comparator agents was determined against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 Pseudomonas aeruginosa. Isolates were consecutively collected from 94 US hospitals, and all isolates were tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories). Enterobacteriaceae isolates resistant to carbapenems (CRE) and/or ceftazidime-avibactam (MIC ≥16 μg/mL) were evaluated for the presence of genes encoding ESBLs, KPC, NDM, and transferable AmpC enzymes. Ceftazidime-avibactam inhibited >99.9% of all Enterobacteriaceae at the susceptible breakpoint of ≤8 μg/mL and was active against multidrug-resistant (MDR; n=2,953; MIC_50/90, 0.25/1 μg/mL; 99.2% susceptible), extensively drug-resistant (XDR; n=448; MIC_50/90, 0.5/2 μg/mL; 97.8% susceptible), and CRE (n=513; MIC_50/90, 0.5/2 μg/mL; 97.5% susceptible) isolates. Only 82.2% of MDR Enterobacteriaceae (n=2,953) and 64.2% of ceftriaxone-nonsusceptible Klebsiella pneumoniae (n=1,063) were meropenem-susceptible. Among Enterobacter cloacae (22.2% ceftazidime-nonsusceptible), 99.8% of isolates, including 99.3% of ceftazidime-nonsusceptible isolates, were ceftazidime-avibactam-susceptible. Only 23 of 36,380 Enterobacteriaceae (0.06%) isolates were ceftazidime-avibactam-nonsusceptible, including 9 metallo-β-lactamase producers and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. Ceftazidime-avibactam showed potent activity against P. aeruginosa (MIC_50/90, 2/4 μg/mL; 97.1% susceptible), including MDR (MIC_50/90, 4/16 μg/mL; 86.5% susceptible) isolates and inhibited 71.8% of isolates nonsusceptible to meropenem, piperacillin-tazobactam, and ceftazidime (n=628). In summary, ceftazidime-avibactam demonstrated potent activity against a large collection (n=44,248) of contemporary gram-negative bacilli isolated from US patients, including organisms resistant to most currently available agents, such as CRE and meropenem-nonsusceptible P. aeruginosa.

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