616. Evaluation of In Vitro Susceptibility to Ceftazidime/Avibactam of Clinical Isolates of Carbapenem Nonsusceptible Gram-Negative Bacilli from Colombia

BACKGROUND: Ceftazidime/avibactam (CZA) is a combination of a third-generation cephalosporin and a diazabicyclooctane β-lactamase inhibitor, which is active against a broad range of class A, C and D β-lactamases. In Colombia, high rates of multidrug-resistant Enterobacteriaceae (Ent)and P. aeruginosa (Pae) have been reported. Of special concern are KPC enzymes endemic in Ent and found in Pae, which are associated with higher mortality and healthcare costs, as well as limited therapeutic options. Herein, we evaluate the susceptibility of clinical isolates of carbapenem nonsusceptible Ent (CNS-E) and Pae (CNS-P) to CZA with the aim of understanding its role as a therapeutic option for these bacteria. METHODS: Three hundred ninety-nine nonduplicate clinical isolates of carbapenem nonsusceptible Gram-negative bacilli were collected in 13 medical centers from 12 Colombian cities, from January 2016 to October 2017 (137 K. pneumoniae [Kpn], 76 E. coli, 34 Enterobacter spp., 21 S. marcescens [Sma] and 131 Pae). CNS-E was defined as minimum inhibitory concentrations (MIC) ≥1 mg/L for ertapenem and CNS-P was defined as MIC ≥4 mg/L for meropenem. MIC were determined by broth microdilution and interpreted according to current CLSI guidelines. CZA MIC were determined using double dilutions of ceftazidime and a fixed concentration of avibactam of 4 mg/L. Comparator agents were ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, tigecycline (TGC), and fosfomycin (FOS). RESULTS: Antimicrobial activity of CZA and comparators is shown in Table 1. CZA susceptibility ranged from 69% in Kpn to 81% in Sma, whereas 49% of CNS-P were susceptible to CZA. In both, CNS-E and CNS-P, CZA was superior to all other tested β-lactam compounds. Notably, in CNS-E CZA susceptibility was comparable to FOS and TGC (except for TGC in Sma). CONCLUSION: CZA is the most active β-lactam against CNS-E and CNS-P. CZA nonsusceptibility suggests the presence of other resistance mechanisms, such as class B β-lactamases that are not inhibited by avibactam, and which are more frequently reported in CNS-P. Our results highlight the key role of new agents such as CZA in KPC endemic countries and the need for surveillance studies to determine the nature of resistance mechanisms. [Image: see text] DISCLOSURES: All authors: No reported disclosures.