Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens

Antimicrob Agents Chemother. 2013 Nov;57(11):5548-58. doi: 10.1128/AAC.01288-13. Epub 2013 Aug 26.

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 (MIC90) 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 (MIC90 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Community-Acquired Infections / drug therapy
  • Community-Acquired Infections / microbiology
  • Cross Infection / drug therapy
  • Cross Infection / microbiology
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Gene Expression
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / microbiology
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / genetics
  • Gram-Positive Bacteria / isolation & purification
  • Gram-Positive Bacterial Infections / drug therapy
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • Tetracyclines / chemistry
  • Tetracyclines / pharmacology*
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • ATP-Binding Cassette Transporters
  • Anti-Bacterial Agents
  • Tetracyclines
  • eravacycline
  • beta-Lactamases