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

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 mu L) of 10(7) 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 log(10) cfu/g) than nafcillin (-1.3 and -1.8 log10 cfu/g), vancomycin (-2.9 and -2.2 log(10) cfu/g) and linezolid (-0.4 and +0.3 log(10) cfu/g). Conclusions: These findings support the potential clinical utility of telavancin in the treatment of MSSA pneumonia.