A multicenter performance evaluation of imipenem-relebactam gradient diffusion susceptibility testing for Pseudomonas aeruginosa

Imipenem-relebactam (I/R) is a beta-lactam/beta-lactamase inhibitor combination given with cilastatin that is indicated for the treatment of complicated urinary tract infections, including pyelonephritis and complicated intra-abdominal infections in patients. Recently, a new gradient diffusion method for antimicrobial susceptibility testing of this antibiotic was developed for Pseudomonas aeruginosa (ETEST IRPA) as an alternative to broth microdilution (BMD). Our objective was to evaluate the performance of the I/R ETEST in comparison to BMD across three external and one internal study sites for 437 (77 challenge, 360 clinical) P. aeruginosa isolates. Using the U.S. Food and Drug Administration (FDA) interpretive breakpoints, ETEST IRPA achieved a 97.7% (427/437) essential agreement (EA), 91.1% (398/437) categorical agreement (CA), 0% very major errors (VMEs), 0.9% (3/329) major errors (MEs), and 8.2% (36/437) minor errors (mEs). Using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) interpretive breakpoints, ETEST IRPA achieved a 97.7% (427/437) EA, 93.8% (410/437) CA, 12% (13/108) VME, and 4.2% (14/329) ME. Both bias and trending were in alignment with regulatory requirements. Reproducibility testing on 10 strains showed 99.6% (269/270) of results were within ±1 doubling dilution of the modal minimum inhibitory concentration (MIC). MIC 50 and MIC 90 values for imipenem were 8 and 32, respectively, in comparison to 1 and 8 with the addition of relebactam as determined by ETEST. In conclusion, ETEST IRPA provides both accurate and reproducible results for performing antimicrobial susceptibility testing of P. aeruginosa when interpreted with both FDA and EUCAST criteria. IMPORTANCE Antimicrobial susceptibility testing is key to proper treatment of bacterial infections. Broth microdilution is the gold standard for antimicrobial susceptibility testing; however, it can be time-consuming and requires high levels of technical expertise. This study evaluates a new gradient diffusion method for antimicrobial susceptibility testing of imipenem-relebactam against Pseudomonas aeruginosa . The findings support the use of imipenem-relebactam gradient diffusion as an accurate and reproducible method of antimicrobial susceptibility testing against Pseudomonas aeruginosa .