Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, against Hospital and Community Pathogens

• DOI: 10.1128/aac.01288-13
• Publication Date: 2013-08-27T04:14:23Z
• Authors: J. A. Sutcliffe; W. O'Brien; C. Fyfe; T. H. Grossman
• Keywords: 0301 basic medicine; Cross Infection; Gene Expression; Microbial Sensitivity Tests; Gram-Positive Bacteria; beta-Lactamases; Anti-Bacterial Agents; 3. Good health; Community-Acquired Infections; 03 medical and health sciences; Tetracyclines; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Humans; ATP-Binding Cassette Transporters; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections

ABSTRACT

Eravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial activity against panels of recently isolated aerobic and anaerobic Gram-negative and Gram-positive bacteria. Eravacycline showed potent broad-spectrum activity against 90% of the isolates (MIC 90 ) in each panel at concentrations ranging from ≤0.008 to 2 μg/ml for all species panels except those of Pseudomonas aeruginosa and Burkholderia cenocepacia (MIC 90 values of 32 μg/ml for both organisms). The antibacterial activity of eravacycline was minimally affected by expression of tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Furthermore, eravacycline was active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance. Eravacycline has the potential to be a promising new intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated hospital/health care infections and moderate-to-severe community-acquired infections.