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

Abstract

Objectives: To assess the efficacy of telavancin, a rapidly bactericidal lipoglycopeptide, and three comparator agents in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus (MSSA). Methods: Female Bagg inbred albino c-strain (BALB/c) mice were rendered neutropenic and infected by intranasal inoculation (50 μ L) of 107 cfu of S. aureus ATCC 29213. Infected mice were then allocated to one of five treatment arms: subcutaneous (sc) telavancin 40 mg/kg every 12 h, sc nafcillin 40 mg/kg every 4 h, sc vancomycin 110 mg/kg every 12 h, intravenous linezolid 80 mg/kg every 12 h or no drug (control group). Test compounds were studied under low and high pre-treatment titre conditions by initiating drug treatment at 4 and 8 h post-inoculation, respectively. Drug doses were calculated to simulate human exposures (area under the curve or t > MIC) at therapeutic doses. Lungs were harvested and homogenized 24 and 48 h after inoculation to determine the bacterial titre. Results: At 48 h post-inoculation in the low and high pre-treatment titre groups, respectively, telavancin produced greater reductions (from pre-treatment values) in bacterial burden (-4.3 and -3.2 log10 cfu/g) than nafcillin (-1.3 and -1.8 log10 cfu/g), vancomycin (-2.9 and -2.2 log10 cfu/g) and linezolid (-0.4 and +0.3 log10 cfu/g). Conclusions: These findings support the potential clinical utility of telavancin in the treatment of MSSA pneumonia. © The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.