Background: Imipenem/Relebactam (IPR), RECARBRIO brand name, is a combination of imipenem, a penem antibacterial, cilastatin, a renal dehydropeptidase inhibitor, and relebactam, a beta-lactamase inhibitor, indicated in patients 18 years of age and older with complicated urinary tract infections (cITU) including pyelonephritis or with complicated intra-abdominal infections (cIAI) caused by susceptible gram-negative bacteria. This study evaluated the performance of ETEST® IPR, a new gradient diffusion strip (FDA cleared but not yet CE marked) for determining antimicrobial susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa as compared to CLSI M07 broth microdilution reference method (BMD).
Materials/methods: A population of 652 isolates including 477 Enterobacteriaceae (30 Citrobacter freundii, 103 Enterobacter cloacae/Enterobacter cloacae complex, 165 Escherichia coli, 30 Klebsiella aerogenes, 32 Klebsiella oxytoca and 117 Klebsiella pneumoniae) and 175 Pseudomonas aeruginosa were tested at 4 clinical trial sites, including one internal laboratory using ETEST® IPR and BMD. Results were analyzed in terms of essential (EA), category (CA) agreements, minor (mE), major (ME) and very major (VME) error rates using FDA breakpoints (Enterobacteriaceae: ≤1/4 (S), 2/4 (I) and ≥4/4 (R) µg/mL, Pseudomonas aeruginosa: ≤2/4 (S), 4/4 (I) and ≥8/4 (R) µg/mL).
Results: Results are summarized in Table 1. ETEST® IPR performance for Pseudomonas aeruginosa met FDA acceptance criteria for EA (≥90%), CA (≥90%), ME (≤3%) and VME (≤2%). For Enterobacteriaceae ETEST® IPR performances met FDA criteria for EA, CA and ME but not for VME with a rate of 2.3% (1/44). That percentage was only due to one Very Major Error with an E. coli isolate. Repeat testing of both ETEST® Imipenem/Relebactam and the reference method with this isolate showed acceptable category agreement between the two tests.
Conclusions: When compared to the reference method, results of this multicenter trial support the accuracy of ETEST® IPR for determining the MIC of Enterobacteriaceae and Pseudomonas aeruginosa in a clinical setting. As such, the new ETEST® IPR can be considered as substantially equivalent to BMD.