LAUSR

Learning Objectives: Pseudomonas aeruginosa (PSA) is a common cause of infections in the intensive care unit (ICU) and notable for extensive antimicrobial resistance. Increasing carbapenem resistance among PSA, limits therapeutic options available to patients. Relebactam is a novel non-β-lactam, β-lactamase inhibitor being developed in combination with imipenem (IPM). Relebactam restores IPM activity against bacteria that produce class A and C β-lactamases, including AmpC-beta-lactamases and Klebsiella pneumoniae carbapenemases. The in vitro activity of imipenem-relebactam (I/R) was evaluated against 232 PSA isolates from hospitalized patients. Methods: Geographically diverse US hospitals provided non-duplicate respiratory and blood PSA isolates collected from patients in the ICU and non-ICU setting between July 2017 and June 2018. Minimum inhibitory concentrations (MICs) for I/R, IPM, and meropenem (MEM) were measured using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methodology. Susceptibility (%S) was defined per CLSI criteria. I/R %S was interpreted using CSLI breakpoints for IPM (susceptible ≤ 2μg/ml; resistant ≥ 8μg/ml). Results: The participating US hospitals contributed 232 non-duplicate PSA isolates. Forty six percent (106/232) of isolates were collected in the ICU; 206/232 (89%) were from a respiratory source. Overall %S to I/R, IPM, and MEM were 83% (192/232), 56% (129/232), and 61% (142/232), respectively. The I/R MIC inhibiting 50% (MIC50) and 90% (MIC90) of isolates was 0.5μg/ ml and 4μg/ml, respectively. The MIC90 for I/R was 8-fold lower compared with the MIC90 for both IPM and MEM (32μg/ml). Among ICU isolates, %S was 79%, 52%, and 59% for I/R, IPM, and MEM, respectively. Of the 109 carbapenem non-susceptible isolates (i.e. IPM or MEM non-susceptible), I/R MIC50, MIC90 and %S was 2μg/ml, 8μg/ml, and 64%, respectively. Relebactam restored susceptibility in 63.1% (65/103) of IPM non-susceptible PSA. Conclusions: Carbapenem non-susceptible PSA was common in these US hospitals. I/R demonstrated potent in vitro activity against these contemporary PSA, including isolates from the ICU as well as those that were carbapenem non-susceptible. These data suggest I/R should have a useful role in the treatment of PSA infections in the ICU.