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In vitro activity of SPR206 and comparator agents against Pseudomonas aeruginosa , Acinetobacter species, and Enterobacterales responsible for infection in United States, European, Israeli, and Turkish hospitals

Year: 2025
Type: article
Abstract: ABSTRACT 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 in vivo safety profiles. This study determined the in vitro activity of SPR206 against a diverse collection of gram-negative isolates. SPR206 was tested against 5,179 Enterobacterales, Pseudomonas aeruginosa , and Acinetobacter 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 50/90 , 0.25/0.25–0.5 mg/L) was active against P. aeruginosa , 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 Acinetobacter spp., including 90.4 and 87.9% of the multidrug-resistant (MIC 50/90 , 0.12/2 mg/L) and extensively drug-resistant (MIC 50/90 , 0.12/8 mg/L) subsets at MIC values of ≤2 mg/L. SPR206 (MIC 50/90 , 0.06/0.25 mg/L) inhibited 95.4% of non-Morganellaceae Enterobacterales at MIC values of ≤2 mg/L. SPR206 MIC 50 and MIC 90 values of 0.06 and 0.5 mg/L were obtained against carbapenem-resistant Enterobacterales from the US and Western Europe, whereas MIC 50 of 0.5 mg/L and MIC 90 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. IMPORTANCE SPR206 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 Acinetobacter spp. and Pseudomonas aeruginosa , 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.
DOI: 10.1128/spectrum.01341-25
Authors: Gina M. Morgan, Ian Critchley, Nicole Cotroneo, Helio Sader, Mariana Castanheira, Rodrigo Mendes
Language: English
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W4414083398
FWCI:
Cites: 19
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Related to: 10