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 language | English |
|---|---|
| Article number | e00004-17 |
| Journal | mSphere |
| Volume | 2 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1 Jan 2017 |
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Keywords
- Community-acquired bacterial pneumonia
- Fluorocycline
- TP-271
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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 journal › Article › Research › peer-review
TY - JOUR
T1 - Fluorocycline TP-271 is potent against complicated community-acquired bacterial pneumonia pathogens
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.
PY - 2017/1/1
Y1 - 2017/1/1
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.
KW - Community-acquired bacterial pneumonia
KW - Fluorocycline
KW - TP-271
UR - http://www.scopus.com/inward/record.url?scp=85031426219&partnerID=8YFLogxK
U2 - 10.1128/mSphere.00004-17
DO - 10.1128/mSphere.00004-17
M3 - Article
VL - 2
JO - mSphere
JF - mSphere
SN - 2379-5042
IS - 1
M1 - e00004-17
ER -