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

Abstract

BackgroundThe in vitro activity of ceftazidime-avibactam (CAZ-AVI) and many comparator agents were tested against various resistant subsets of organisms selected among 36,380 Enterobacteriaceae and 7,868 P. aeruginosa isolates.MethodsIsolates were consecutively collected from 94 US hospitals in 2013–2016 and tested for susceptibility by reference broth microdilution methods in a central monitoring laboratory (JMI Laboratories) as part of the International Network for Optimal Resistance Monitoring (INFORM) program. Enterobacteriaceae strains with elevated CAZ-AVI MIC values (≥16 μg/mL) were evaluated for the presence of genes encoding extended-spectrum β-lactamases, KPC, NDM, and transferable AmpC enzymes.ResultsCAZ-AVI inhibited >99.9% of all Enterobacteriaceae at the susceptible (S) breakpoint of ≤8 μg/mL and was active against multidrug-resistant (MDR; n = 2,953; MIC50/90, 0.25/1 μg/mL; 99.2%S, extensively drug-resistant (XDR; n = 448; MIC50/90, 0.5/2 μg/mL; 97.8%S), and carbapenem-resistant isolates (CRE; n = 513; MIC50/90, 0.5/2 μg/mL; 97.5%S). Only 82.2% of MDR Enterobacteriaceae and 64.2% of ceftriaxone-nonsusceptible (NS) Klebsiella pneumoniae (n = 1,063) were meropenem-S. Among Enterobacter cloacae (n = 3,740; 22.2% ceftazidime-NS), 99.8% of isolates, including 99.3% of ceftazidime-NS isolates, were CAZ-AVI-S. Only 22 of 36,380 Enterobacteriaceae (0.06%) isolates were CAZ-AVI-NS, including 8 MBL-producers (0.02%) and 2 KPC-producing strains with porin alteration; the remaining 12 strains showed negative results for all β-lactamases tested. CAZ-AVI showed potent activity against P. aeruginosa (n = 7,868; MIC50/90, 2/4 μg/mL; 97.1% S), including meropenem-NS (n = 1,471; MIC50/90, 4/16 μg/mL; 87.2%S) and MDR (n = 1,562; MIC50/90, 4/16 μg/mL; 86.5%S) isolates, and inhibited 71.8% of isolates NS to meropenem, piperacillin-tazobactam, and ceftazidime (n = 628).ConclusionCAZ-AVI demonstrated potent activity against a large US collection (n = 44,248) of contemporary gram-negative bacilli, including organisms resistant to most currently available agents, such as CRE and meropenem-NS P. aeruginosa.Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; M. Castanheira, Allergan: Research Contractor, Research grant; D. Shortridge, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant