Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens

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 pathogen...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	TP-271 community-acquired bacterial pneumonia fluorocycline Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fc839a5a5190439892aac4f57b1d746e
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spelling	oai:doaj.org-article:fc839a5a5190439892aac4f57b1d746e2021-11-15T15:22:03ZFluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens10.1128/mSphere.00004-172379-5042https://doaj.org/article/fc839a5a5190439892aac4f57b1d746e2017-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00004-17https://doaj.org/toc/2379-5042ABSTRACT 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. IMPORTANCE Rising resistance rates for macrolides, fluoroquinolones, and β-lactams in the most common pathogens associated with community-acquired bacterial pneumonia (CABP) are of concern, especially for cases of moderate to severe infections in vulnerable populations such as the very young and the elderly. New antibiotics that are active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus are needed for use in the empirical treatment of the most severe forms of this disease. TP-271 is a promising new fluorocycline antibiotic demonstrating in vitro potency and nonclinical efficacy by intravenous and oral administration against the major pathogens associated with moderate to severe CABP.Trudy H. GrossmanCorey FyfeWilliam O’BrienMeredith HackelMary Beth MinyardKen B. WaitesJacques DuboisTimothy M. MurphyAndrew M. SleeWilliam J. WeissJoyce A. SutcliffeAmerican Society for MicrobiologyarticleTP-271community-acquired bacterial pneumoniafluorocyclineMicrobiologyQR1-502ENmSphere, Vol 2, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	TP-271 community-acquired bacterial pneumonia fluorocycline Microbiology QR1-502
spellingShingle	TP-271 community-acquired bacterial pneumonia fluorocycline Microbiology QR1-502 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 Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens
description	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. IMPORTANCE Rising resistance rates for macrolides, fluoroquinolones, and β-lactams in the most common pathogens associated with community-acquired bacterial pneumonia (CABP) are of concern, especially for cases of moderate to severe infections in vulnerable populations such as the very young and the elderly. New antibiotics that are active against multidrug-resistant Streptococcus pneumoniae and Staphylococcus aureus are needed for use in the empirical treatment of the most severe forms of this disease. TP-271 is a promising new fluorocycline antibiotic demonstrating in vitro potency and nonclinical efficacy by intravenous and oral administration against the major pathogens associated with moderate to severe CABP.
format	article
author	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
author_facet	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
author_sort	Trudy H. Grossman
title	Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens
title_short	Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens
title_full	Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens
title_fullStr	Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens
title_full_unstemmed	Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens
title_sort	fluorocycline tp-271 is potent against complicated community-acquired bacterial pneumonia pathogens
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/fc839a5a5190439892aac4f57b1d746e
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Fluorocycline TP-271 Is Potent against Complicated Community-Acquired Bacterial Pneumonia Pathogens

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