activity of SPR206 and comparator agents against , species, and Enterobacterales responsible for infection in United States, European, Israeli, and Turkish hospitals.

Increasing rates of antimicrobial resistance require additional safe and effective options for managing difficult-to-treat infections. SPR206 is a next-generation polymyxin with improved safety profiles. This study determined the activity of SPR206 against a diverse collection of gram-negative isolates. SPR206 was tested against 5,179 Enterobacterales, , and spp. collected from patients in the United States (US), Europe, Israel, and Turkey. Broth microdilution was performed following the Clinical & Laboratory Standards Institute (CLSI) guidelines, and MIC results interpreted by CLSI, European Committee on Antimicrobial Susceptibility Testing (EUCAST), and United States Food and Drug Administration (US FDA) criteria. SPR206 (MIC, 0.25/0.25-0.5 mg/L) was active against , including the multidrug-resistant, extensively drug-resistant, and difficult-to-treat subsets, with 99.8-100% of isolates inhibited at MIC values of ≤2 mg/L. SPR206 inhibited 94.5% of spp., including 90.4 and 87.9% of the multidrug-resistant (MIC, 0.12/2 mg/L) and extensively drug-resistant (MIC, 0.12/8 mg/L) subsets at MIC values of ≤2 mg/L. SPR206 (MIC, 0.06/0.25 mg/L) inhibited 95.4% of non-Morganellaceae Enterobacterales at MIC values of ≤2 mg/L. SPR206 MIC and MIC values of 0.06 and 0.5 mg/L were obtained against carbapenem-resistant Enterobacterales from the US and Western Europe, whereas MIC of 0.5 mg/L and MIC of 64 mg/L were noted against carbapenem-resistant Enterobacterales isolates from Eastern Europe. SPR206 demonstrated potent activity against a large collection of gram-negative organisms, including resistant subsets. These results, along with an enhanced safety profile, warrant the development of SPR206 as a candidate for the treatment of infections caused by gram-negative bacteria.IMPORTANCESPR206 is a novel, next-generation polymyxin with improved safety profiles that demonstrates activity against gram-negative organisms. This study benchmarks the activity and spectrum of SPR206 against a large collection of gram-negative isolates, including multidrug-resistant and extensively drug-resistant spp. and , and carbapenem-resistant Enterobacterales collected from multiple medical sites in the US and Europe. Additional treatment options are needed as antimicrobial resistance emerges and spreads. The results presented in this manuscript show potent SPR206 activity against resistant and difficult-to-treat gram-negative organisms.