690. Activity of a Novel Polymyxin Analog, QPX9003, Tested Against Resistant Gram-Negative Pathogens, Including Carbapenem-Resistant Acinetobacter, Enterobacterales, and Pseudomonas

Abstract Background Multidrug resistance (MDR) among Gram-negative (GN) organisms and the limited active therapeutic options against these pathogens are matters of worldwide concern. Polymyxins are cationic peptides that act on the bacterial cell membrane and have good activity against GN organisms, including MDR strains. We evaluated the activity of QPX9003, a novel polymyxin analog with an improved safety profile over current polymyxins, against a large collection of resistant GN isolates collected worldwide. Methods Susceptibility testing was performed by reference microbroth dilution against 2,518 GN organisms for QPX9003, colistin (COL), levofloxacin, tigecycline, gentamicin, amikacin, meropenem, cefepime, piperacillin–tazobactam, and ceftazidime–avibactam. Isolates included 1,000 Pseudomonas aeruginosa (PSA) enriched for MDR, 503 carbapenem-resistant Acinetobacter baumannii (CRAB), and 1,105 Enterobacterales (ENT). Results QPX9003 had potent activity against PSA isolates enriched for resistance against β-lactam/β-lactamase inhibitor combinations and was 4-fold more potent than COL (MIC50/90, 0.25/0.25 mg/L vs. MIC50/90 of 1/1 mg/L). QPX9003 was also more potent than COL against the panel of CRAB with MIC50/90 of 0.125/1 mg/L and 0.5/4 for QPX9003 and COL, respectively. QPX9003 had a modal MIC of 0.06 mg/L against a large collection of ENT isolates resistant to cephalosporins and/or carbapenems (MIC50/90, 0.06/16 mg/L). QPX9003 activity was identical against 508 carbapenem-resistant Enterobacterales (CRE; MIC50/90, 0.06/16 mg/L) isolates and 511 Klebsiella pneumoniae isolates (MIC50/90, 0.06/16 mg/L) in this collection. Escherichia coli isolates were considerably more sensitive to QPX9003 (MIC50/90, 0.06/0.12 mg/L) compared with K. pneumoniae isolates. Activity of QPX9003 and COL was similar against ENT. Other comparator agents had limited activity against PSA, CRAB, and CRE isolates. Conclusion QPX9003 had activity against this collection of highly resistant GN isolates and was particularly active against the PSA and CRAB isolates. QPX9003 is a promising new-generation polymyxin agent. Disclosures All authors: No reported disclosures.