In vitro activity of RX-P873 against enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii

Abstract

RX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shown in vitro activity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.Enterobacteriaceae (657), Pseudomonas aeruginosa (200), and Acinetobacter baumannii (202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were tested in vitro by broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC 90,μg/ml) was > 32-fold more active than ceftazidime and inhibited 97.1% and 99.5% of Enterobacteriaceae isolates at MIC values of ≤ 1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of > 4 μg/ml (all were indole-positive Protea). RX-P873 (MIC 50/90, 2/4 μg/ml) was highly active against Pseudomonas aeruginosa isolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active against P. aeruginosa than tobramycin (MIC 90, 2 μg/ml; 91.0% susceptible) and colistin (MIC 90, 2μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC 90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC 90, 8μg/ml; 76.0% susceptible). RX-P873, the most active agent against Acinetobacter baumannii (MIC 90, 1 μg/ml), was 2-fold more active than colistin (MIC 90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC 90, 4 μg/ml). This novelagent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.