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BAY 73-7388, a novel aminomethylcycline, exhibits potent efficacy in pulmonary murine models of infection

Abstract number: 902_p927

McKenney D.

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Objective:

With the emergence of resistance to currently available antibiotics in the treatment of infectious diseases, the development of novel antibiotic classes has become of major importance. BAY 73-7388 is the first aminomethylcycline antibacterial agent and is characterised by potent activity in vitro against sensitive and multi-antibiotic resistant Gram-positive, Gram-negative and atypical bacteria. We have evaluated BAY 73-7388 in several murine pulmonary infection models with a range of pathogens in both neutropenic (Neut) and immunocompetent (IC) mice.

Methods:

BAY 73-7388 and reference antibiotics were evaluated in acute, systemic lethal infections caused by multi-resistant (res) and susceptible (sus) Streptococcus pneumoniae (Spn); acute, lethal pulmonary Spn infection in Neut mice; chronic, Spn lung model in IC mice; and chronic Haemophilus influenzae (Hflu) infection model in IC mice. In each infection BAY 73-7388 and other antibiotics were administered i.v.

Results:

PD50 (survival) and ED50 (bacterial burden) results for BAY 73-7388 and comparators, vancomycin (VAN), linezolid (LIN), ciprofloxacin (CIP), azithromycin (AZI) and doxycycline (DOX) against sus and res strains of Spn and Hflu (sus), are detailed in the table below.

Conclusions:

Overall, BAY 73-7388 performed as well or better than the currently available therapeutic agents in all the models investigated in this study.

(BAY 73-7388 was discovered by Paratek Pharmaceuticals Inc., Boston, MA, and designated PTK 0796.)

Table 1.  

In vivo modelEfficacy (mg/kg)
BAY 73-7388 AZI CIP LIN VAN DOX 
Acute, systemic Spn, IC (sus) (PD50)0.092.21>503.51.41.8
Acute, systemic Spn, Neut (res) (PD50)0.1418.921.37.10.14>50
Chronic Spn,IC (ED50)7.45.15>50>40>4031.6
Chronic Hflu,IC (ED50)4.731.61.0NANA18.6
Acute, pulmonary Spn, Neut (PD50)11.07.531.6>407.2>50
Acute, pulmonary Spn, Neut (res) (PD50)8.5>50>50>405.4>50
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Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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