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Efficacy of telavancin in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus

Abstract number: 1733_1271

Hegde S., Reyes N., Skinner R., Difuntorum S.

Objectives: Telavancin, a novel, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action against Gram-positive bacteria (including methicillin-resistant Staphylococcus aureus [MRSA]), exhibited efficacy in a murine model of pneumonia caused by MRSA in a previous study. The objective of the current investigation was to evaluate the efficacy of telavancin in a murine model of pneumonia induced by methicillin-susceptible S. aureus (MSSA) in comparison with three other antimicrobial agents.

Methods: Female Bagg inbred albino c-strain (BALB/c) mice, weighing 18–20 g, were rendered neutropenic with two intraperitoneal doses of cyclophosphamide 250 mg/kg administered 4 and 2 days prior to infection. Mice were infected with an intranasal inoculation (50 microL) of 107 colony-forming units of MSSA strain ATCC 29213. Infected mice were then allocated to one of five treatment arms: telavancin 40 mg/kg subcutaneously (SC) every 12 hours, nafcillin 40 mg/kg SC every 4 hours, linezolid 80 mg/kg intravenously every 12 hours, vancomycin 110 mg/kg SC every 12 hours, or no drug (control group). Treatment was initiated at either 4 or 8 hours post-inoculation. Drug doses were calculated to simulate human exposures (area under the curve or time >MIC) at therapeutic doses. Lungs were harvested and homogenised 24 and 48 hours after inoculation to determine the bacterial titre using trypsin-soy agar plates containing aztreonam 1.0 mg/mL (to select for MSSA).

Results: Telavancin demonstrated potent bactericidal activity against MSSA strain ATCC 29213 in vitro in terms of MIC, and in vivo in terms of reduction in lung bacterial titre, compared with nafcillin, linezolid and vancomycin (Table).

Table. MICs and lung bacterial titresa

TreatmentMIC (mg/mL)Change in lung bacterial titre (log CFU/g) (n = 6)
4 hb8 hb  
Telavancin0.5-4.3†‡-3.2†§
Nafcillin0.25-1.4-1.8
Linezolid2-0.40.3
Vancomycin1-2.9-2.2
aMIC, minimum inhibitory concentration; CFU, colony-forming units.
bTime (post-inoculation) of treatment initiation.
P < 0.05 vs pre-treatmen titre; P < 0.05 vs nafcillin, vancomycin and linezolid; §P < 0.05 vs nafcillin and vancomycin.

Conclusion: The data from the present study demonstrate the efficacy of telavancin in reducing lung bacterial burden in an MSSA model of pneumonia in neutropenic mice. The reduction in lung bacterial titre with telavancin was significantly greater than with nafcillin, vancomycin and linezolid.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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