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In Vitro Potency and Spectrum of the Novel Polymyxin MRX-8 Tested against Clinical Isolates of Gram-Negative Bacteria
10.1128/aac.00139-22
Leonard R. Duncan
Wen Wang
Helio S. Sader
Susceptibility
Susceptibility
polymyxin
colistin
lipopeptide
Gram-negative
resistance
MRX-8
American Society for Microbiology
American Society for Microbiology
Copyright © 2022 American Society for Microbiology.
All Rights Reserved.
20220427
2022
ABSTRACT
The polymyxins display excellent in vitro antimicrobial activity against most Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii isolates, but their clinical utility has been limited because of class-specific toxicity problems. Therefore, new polymyxin analogs with improved safety properties are needed to combat serious infections caused by resistant Gram-negative pathogens. MRX-8 is a novel polymyxin B analog that displays reduced toxicity in in vitro and animal assays and is currently being evaluated in a phase 1 clinical trial. In this nonclinical study, the in vitro potency and spectrum of MRX-8 and comparators were evaluated against a large set of Gram-negative clinical isolates collected in the United States in 2017 to 2020. MRX-8, colistin, and polymyxin B exhibited nearly identical antimicrobial activities against the Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii isolate sets. MRX-8 MIC50 and MIC90 values were 0.12 and 0.25 mg/L, respectively, for the set of Enterobacterales isolates not intrinsically resistant to colistin and 0.5 and 1 mg/L, respectively, against both the A. baumannii and P. aeruginosa isolate sets. All three polymyxin-class compounds retained activity against meropenem-resistant and multidrug-resistant isolate subsets but were inactive against isolates displaying acquired or intrinsic resistance to polymyxins. These results support the continued development of MRX-8 to treat serious Gram-negative infections.
20220128
20220405
1098-6596
Adobe LiveCycle PDF Generator; modified using iText® 5.5.13.2 ©2000-2020 iText Group NV (AGPL-version)2022-05-23T07:17:08-07:00
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