title: In vitro susceptibility of β-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE) to eravacycline.
abstract: Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class being developed for the treatment of complicated urinary tract infections and complicated intra-abdominal infections. Eravacycline has activity against many key Gram-negative pathogens, including Enterobacteriaceae resistant to carbapenems, cephalosporins, fluoroquinolones and β-lactam/β-lactamase inhibitor combinations, including strains that are multidrug-resistant. Carbapenem-resistant Enterobacteriaceae (CRE) isolates from 2010 to 2013 (n=110) were characterized for carbapenemase genes by PCR and sequencing. MICs for eravacycline, tetracycline, tigecycline, amikacin, imipenem, ceftazidime, cefotaxime and levofloxacin were determined in broth microdilution assays. All isolates produced at least one carbapenemase, most frequently KPC-3. Nine isolates produced both a KPC serine carbapenemase and a metallo-β-lactamase, NDM-1 (n=1) or VIM-1 (n=8). The 110 isolates were highly resistant to all the β-lactams tested and to levofloxacin, and had MIC50/MIC90 values in the intermediate range for tetracycline and amikacin. MIC50/MIC90 values for eravacycline were 1/2 μg ml(-1) compared with 2/2 μg ml(-1) for tigecycline. Eravacycline MICs were often twofold lower than for tigecycline, with 64% of the eravacycline MICs <2 μg ml(-1) as compared with <4% of tigecycline MICs. Overall, eravacycline demonstrated the lowest cumulative MICs against this panel of recent CRE and may have the potential to treat infections caused by CRE.
authors.affiliation: Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN, USA.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lin
authors.affiliation: Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Bush
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D016133:Polymerase Chain Reaction; D013754:Tetracyclines / Q000008:administration & dosage / Q000494:pharmacology*; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013754:Tetracyclines; C571179:eravacycline; D001618:beta-Lactamases