Activity of rx-04 pyrrolocytosine protein synthesis inhibitors against multidrug-resistant gram-negative bacteria

Abstract

Pyrrolocytosines RX-04A to -D are designed to bind to the bacterial 50S ribosomal subunit differently from currently used antibiotics. The four analogs had broad anti-Gram-negative activity: RX-04A—the most active analog—inhibited 94.7% of clinical Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa at 0.5 to 4 g/ml, with no MICs of 8 g/ml. MICs for multidrug-resistant (MDR) carbapenemase producers were up to 2-fold higher than those for control strains; values were highest for one Serratia isolate with porin and efflux lesions. mcr-1 did not affect MICs.