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BAY 73-7388 demonstrates greater activity than linezolid in a range of murine models of skin and soft tissue infection

Abstract number: 902_p929

Ladel C.H.

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BAY 73-7388 is a novel antibiotic compound being developed for the treatment of severe bacterial infections. It is the first compound selected from the novel class of aminomethylcyclines and was designed to meet an increasingly significant need for additional therapies for treatment of infections, including those resistant to currently available antibiotics. The efficacy of BAY 73-7388 in different mouse models of skin and soft tissue infection (SSTI) was compared with that of vancomycin (VAN) and linezolid (LIN).

Methods:

Two mouse models were employed to determine the efficacy of BAY 73-7388: (1) infected abscess model (induced by implantation and subsequent infection of Gelfoam (TM)) and (2) infected thigh muscle model in neutropenic mice. Staphylococcus aureus strain DSM11823 (MSSA) was used to infect the respective structures in the skin and soft tissues. Infected abscess bearing mice were treated i.v. bid for 2 days, while thigh muscle infection model mice were treated s.c. 30 min post-infection. CFU reduction of infected tissues and bacterial load in different organs (spread from the infection site) were used as read-out for therapeutic efficacy.

Results:

As measured by reduction of bacterial load, therapy of infected abscesses with BAY 73-7388 (CFU reduction >4 log units at 10 mg/kg) was superior to VAN and LIN (no reduction in bacterial load). Furthermore, BAY 73-7388 reduced the overall bacterial load in spleen, liver, lung and heart. In the reduction of organ load, BAY 73-7388 was as efficacious as VAN or LIN. In the mouse thigh muscle infection model, BAY 73-7388 proved to be as least as effective as VAN (2 log CFU reduction) and superior to LIN, which demonstrated no efficacy at the same dose (0.5 log CFU increase).

Conclusions:

BAY 73-7388 was clearly more potent than LIN and VAN in the infected abscess model, and more potent than LIN and at least as effective as VAN in the thigh wound model.

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

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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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