In vitro activity of NOSO-502, a novel-action antimicrobial, against clinical strains of Enterobacterales including MDR strains.

Background: NOSO-502 belongs to a new class of cationic peptide antimicrobials-the odilorhabdins-which have a novel mechanism of action inhibiting protein synthesis. NOSO-502 is in preclinical development for the treatment of difficult-to-treat MDR Gram-negative infections.

Methods: A total of 360 Enterobacterales were tested against NOSO-502 and comparators using the ISO reference microdilution method. The test panel was derived from clinical isolates and enriched with MDR strains including carbapenemase producers. Time-kill experiments were performed with NOSO-502 and two comparator agents over 24 h at MIC×1 to MIC×16 concentrations.

Results: NOSO-502 demonstrated potent in vitro activity against Escherichia coli (MIC50/90 2/4 mg/L), Klebsiella pneumoniae (MIC50/90 0.5/1 mg/L), Enterobacter spp. and Citrobacter spp. strains (both MIC50/90 1/2 mg/L). MIC50/90 values for Proteus mirabilis were >64/>64 mg/L. None of ESBL production, meropenem non-WT susceptibility, MDR phenotype or the presence of NDM, KPC, OXA, IMP or VIM carbapenemases impacted on the activity of NOSO-502. In time-kill curves, NOSO-502 showed concentration-dependent killing of E. coli, Klebsiella spp. and C. freundii.

Conclusions: NOSO-502 showed potent in vitro inhibitory and bactericidal activity against a panel of Enterobacterales enriched for resistant phenotypes for which there are few therapeutic choices. These findings need to be placed in context with the appropriate pharmacokinetic and dynamic characteristics of NOSO-502.