Potency and Spectrum of the Novel Polymyxin MRX-8 Tested against Clinical Isolates of Gram-Negative Bacteria.

The polymyxins display excellent antimicrobial activity against most , 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 and animal assays and is currently being evaluated in a phase 1 clinical trial. In this nonclinical study, the 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 , Pseudomonas aeruginosa, and Acinetobacter baumannii isolate sets. MRX-8 MIC and MIC values were 0.12 and 0.25 mg/L, respectively, for the set of 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.