Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens

Trudy H. Grossman, Corey Fyfe, William O'Brien, Meredith Hackel, Mary Beth Minyard, Ken B. Waites, Jacques Dubois, Timothy M. Murphy, Andrew M. Slee, William J. Weiss, Joyce A. Sutcliffe

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Abstract

TP-271 is a novel, fully synthetic fluorocycline antibiotic in clinical development for the treatment of respiratory infections caused by susceptible and multidrug-resistant pathogens. TP-271 was active in MIC assays against key community respiratory Gram-positive and Gram-negative pathogens, including Streptococcus pneumoniae (MIC90 = 0.03 μg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC90 = 0.25 μg/ml), methicillin-resistant S. aureus (MRSA; MIC90 = 0.12 μg/ml), Streptococcus pyogenes (MIC90 = 0.03 μg/ml), Haemophilus influenzae (MIC90 = 0.12 μg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 μg/ml). TP-271 showed activity (MIC90 = 0.12 μg/ml) against community-acquired MRSA expressing Panton- Valentine leukocidin (PVL). MIC90 values against Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae were 0.004, 1, and 4 μg/ml, respectively. TP-271 was efficacious in neutropenic and immunocompetent animal pneumonia models, generally showing, compared to the burden at the start of dosing, ~2 to 5 log10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log10 CFU reductions when given orally (p.o.). TP-271 was potent against key community-acquired bacterial pneumonia (CABP) pathogens and was minimally affected, or unaffected, by tetracycline-specific resistance mechanisms and fluoroquinolone or macrolide drug resistance phenotypes.

Original languageEnglish
Article numbere00004-17
JournalmSphere
Volume2
Issue number1
DOIs
StatePublished - 1 Jan 2017

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Keywords

  • Community-acquired bacterial pneumonia
  • Fluorocycline
  • TP-271

Cite this

Grossman, T. H., Fyfe, C., O'Brien, W., Hackel, M., Minyard, M. B., Waites, K. B., Dubois, J., Murphy, T. M., Slee, A. M., Weiss, W. J., & Sutcliffe, J. A. (2017). Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens. mSphere, 2(1), [e00004-17]. https://doi.org/10.1128/mSphere.00004-17