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 microL) 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 log(10) 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.
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 microL) 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 log(10) 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.
Authors: Roger V Ortines; Yu Wang; Haiyun Liu; Dustin A Dikeman; Bret L Pinsker; Robert J Miller; Sophia E Kim; Nicole E Ackerman; Joe F Rizkallah; LeeAnn T Marcello; Taylor S Cohen; Christine Tkaczyk; Bret R Sellman; Lloyd S Miller Journal: Antimicrob Agents Chemother Date: 2019-07-25 Impact factor: 5.191
Authors: Christopher S Lunde; Charles H Rexer; Stephanie R Hartouni; Sabine Axt; Bret M Benton Journal: Antimicrob Agents Chemother Date: 2010-02-22 Impact factor: 5.191
Authors: Alyssa G Ashbaugh; Xuesong Jiang; Jesse Zheng; Andrew S Tsai; Woo-Shin Kim; John M Thompson; Robert J Miller; Jonathan H Shahbazian; Yu Wang; Carly A Dillen; Alvaro A Ordonez; Yong S Chang; Sanjay K Jain; Lynne C Jones; Robert S Sterling; Hai-Quan Mao; Lloyd S Miller Journal: Proc Natl Acad Sci U S A Date: 2016-10-24 Impact factor: 11.205