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 Weiss, Joyce A. Sutcliffe

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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 (MIC 90 = 0.03 μg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC 90 = 0.25 μg/ml), methicillin-resistant S. aureus (MRSA; MIC 90 = 0.12 μg/ml), Streptococcus pyogenes (MIC 90 = 0.03 μg/ml), Haemophilus influenzae (MIC 90 = 0.12 μg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 μg/ml). TP-271 showed activity (MIC 90 = 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 log 10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log 10 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

Fingerprint

Bacterial Pneumonia
Methicillin-Resistant Staphylococcus aureus
Haemophilus influenzae
Streptococcus pneumoniae
Haemophilus Infections
Tetracycline Resistance
Moraxella (Branhamella) catarrhalis
Legionella pneumophila
Chlamydophila pneumoniae
Mycoplasma pneumoniae
Methicillin
Streptococcus pyogenes
Fluoroquinolones
Macrolides
Drug Resistance
Respiratory Tract Infections
Staphylococcus aureus
Pneumonia
Animal Models
Anti-Bacterial Agents

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., ... 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
Grossman, Trudy H. ; Fyfe, Corey ; O'Brien, William ; Hackel, Meredith ; Minyard, Mary Beth ; Waites, Ken B. ; Dubois, Jacques ; Murphy, Timothy M. ; Slee, Andrew M. ; Weiss, William ; Sutcliffe, Joyce A. / Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens. In: mSphere. 2017 ; Vol. 2, No. 1.
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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 (MIC 90 = 0.03 μg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC 90 = 0.25 μg/ml), methicillin-resistant S. aureus (MRSA; MIC 90 = 0.12 μg/ml), Streptococcus pyogenes (MIC 90 = 0.03 μg/ml), Haemophilus influenzae (MIC 90 = 0.12 μg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 μg/ml). TP-271 showed activity (MIC 90 = 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 log 10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log 10 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.",
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Grossman, TH, Fyfe, C, O'Brien, W, Hackel, M, Minyard, MB, Waites, KB, Dubois, J, Murphy, TM, Slee, AM, Weiss, W & Sutcliffe, JA 2017, 'Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens', mSphere, vol. 2, no. 1, e00004-17. https://doi.org/10.1128/mSphere.00004-17

Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens. / Grossman, Trudy H.; Fyfe, Corey; O'Brien, William; Hackel, Meredith; Minyard, Mary Beth; Waites, Ken B.; Dubois, Jacques; Murphy, Timothy M.; Slee, Andrew M.; Weiss, William; Sutcliffe, Joyce A.

In: mSphere, Vol. 2, No. 1, e00004-17, 01.01.2017.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Grossman, Trudy H.

AU - Fyfe, Corey

AU - O'Brien, William

AU - Hackel, Meredith

AU - Minyard, Mary Beth

AU - Waites, Ken B.

AU - Dubois, Jacques

AU - Murphy, Timothy M.

AU - Slee, Andrew M.

AU - Weiss, William

AU - Sutcliffe, Joyce A.

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N2 - 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 (MIC 90 = 0.03 μg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC 90 = 0.25 μg/ml), methicillin-resistant S. aureus (MRSA; MIC 90 = 0.12 μg/ml), Streptococcus pyogenes (MIC 90 = 0.03 μg/ml), Haemophilus influenzae (MIC 90 = 0.12 μg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 μg/ml). TP-271 showed activity (MIC 90 = 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 log 10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log 10 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.

AB - 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 (MIC 90 = 0.03 μg/ml), methicillin-sensitive Staphylococcus aureus (MSSA; MIC 90 = 0.25 μg/ml), methicillin-resistant S. aureus (MRSA; MIC 90 = 0.12 μg/ml), Streptococcus pyogenes (MIC 90 = 0.03 μg/ml), Haemophilus influenzae (MIC 90 = 0.12 μg/ml), and Moraxella catarrhalis (MIC90 ≤0.016 μg/ml). TP-271 showed activity (MIC 90 = 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 log 10 CFU reductions against MRSA, S. pneumoniae, and H. influenzae infections when given intravenously (i.v.) and ~1 to 4 log 10 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.

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Grossman TH, Fyfe C, O'Brien W, Hackel M, Minyard MB, Waites KB et al. Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens. mSphere. 2017 Jan 1;2(1). e00004-17. https://doi.org/10.1128/mSphere.00004-17