2051. Relebactam enhances Imipenem activity across the Imipenem susceptibility spectrum among Pseudomonas aeruginosa isolates collected in the United States--SMART 2018-2020

Abstract

Abstract Background The Beta-Lactamase Inhibitors (BLIs) Relebactam (REL) and Avibactam (AVI) both inhibit class A and C beta-lactamases and are approved in combination with the beta-lactam antibiotics imipenem (IMI/REL) and ceftazidime (CAZ/AVI), respectively. Our goal was to evaluate the effect of these BLIs on susceptibility of Pseudomonas aeruginosa isolates that are either nonsusceptible (NS), Intermediate (I) or Susceptible (S) to the partner beta-lactam antibiotic. Methods In 2018-2020, ∼20 unique participating sites in the United States each collected up to 250 consecutive aerobic gram-negative isolates per year (50 each from urine, intraabdominal and blood; 100 from lower respiratory tract). Susceptibility to Imipenem (IMI) and Ceftazidime (CAZ) were determined alone as well as in combination with their cognate BLIs. MICs were determined using broth microdilution and evaluated by CLSI interpretive criteria. Results A total of 2,537 P. aeruginosa isolates were evaluated. Among IMI-NS isolates (MIC >2 μg/mL) REL restored IMI susceptibility to 75% and among CAZ-NS isolates (MIC >8 μg/mL) AVI restored CAZ susceptibility to 73%. For IMI-I isolates (MIC of 4 μg/mL), the presence of REL restored susceptibility to 98%, and 95% had MICs at least one dilution less than the susceptible breakpoint. For CAZ-I isolates (MIC of 16 μg/mL), AVI restored susceptibility to 84% of isolates, and 62% had MICs at least one dilution below the susceptible breakpoint. The addition of REL shifted the mode IMI MIC of IMI-S (MIC ≤ 2 μg/mL) isolates 4-fold, from 2 to 0.5 μg/mL, whereas there was no change in the mode CAZ MIC of CAZ-S (MIC ≤ 8 μg/mL) isolates in the presence of AVI. Conclusion Both REL and AVI restore susceptibility to P. aeruginosa isolates nonsusceptble to their cognate beta-lactam antibiotics (IMI and CAZ, respectively). However, REL had greater enhancement of IMI towards IMI-I isolates when compared to the effect of AVI on CAZ towards CAZ-I isolates. REL substantially enhances IMI activity towards IMI-S isolates whereas no such enhancement was observed for AVI upon CAZ activity towards CAZ-S isolates. REL is differentiated by its ability to enhance the activity of the cognate beta-lactam (IMI) across the susceptibility spectrum. Disclosures Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds.