scholarly journals Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus (MRSA)

2021 ◽  
Author(s):  
David B. Huang ◽  
Eric Gaukel ◽  
Nancy Kerzee ◽  
Katyna Borroto-Esoda ◽  
Simon Lowry ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Infective Endocarditis ◽  
Aortic Valve ◽  
Clinical Evaluation ◽  
Adjunctive Therapy ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Rabbit Model ◽  
Target Tissue ◽  
Methicillin Resistant ◽  
Highly Effective

We utilized the rabbit model of aortic valve infective endocarditis to examine the combined efficacy of the lysin, LSVT-1701, plus daptomycin. The combination of LSVT-1701 plus daptomycin was highly effective at reducing target tissue MRSA counts. When given for four daily doses, both lysin dose-regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as adjunctive therapy for the treatment of invasive MRSA infections.

scholarly journals Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus (MRSA)

2021 ◽  
Author(s):  
David Huang ◽  
Eric Gaukel ◽  
Nancy Kerzee ◽  
Katyna Borroto-Esoda ◽  
Simon Lowry ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Single Dose ◽  
Infective Endocarditis ◽  
Aortic Valve ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Rabbit Model ◽  
Standard Of Care ◽  
Target Tissue ◽  
Daily Dose ◽  
Phage Lysins

MRSA endovascular infections are frequently recalcitrant to treatment with standard-of-care antibiotics. Anti-staphylococcal phage lysins represent important candidate adjunctive agents against invasive MRSA infections because of both their microbicidal and anti-biofilm properties. We utilized the rabbit model of aortic valve infective endocarditis (using the prototype MRSA strain, MW2) to examine the combined efficacy of the lysin, LSVT-1701, plus daptomycin. LSVT-1701 was given at two dose-regimens (32.5 mg/kg and 50 mg/kg) with different dose-durations (single dose vs daily dose for 2 d vs daily dose for 4 d); daptomycin was given at a sub-lethal daily dose of 4 mg/kg for 4 d to maximize potential synergistic interaction outcomes. The combination of LSVT-1701 plus daptomycin was highly effective at reducing target tissue MRSA counts (cardiac vegetations, kidneys, and spleen), especially when the lysin was given for multiple days and/or at higher daily doses. Of importance, when given for four daily doses, both lysin dose-regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as adjunctive therapy for the treatment of invasive MRSA infections.

scholarly journals Efficacy of Telavancin in a Rabbit Model of Aortic Valve Endocarditis Due to Methicillin-Resistant Staphylococcus aureus or Vancomycin-Intermediate Staphylococcus aureus

2005 ◽  
Vol 49 (8) ◽  
pp. 3163-3165 ◽  
Author(s):  
Andres G. Madrigal ◽  
Li Basuino ◽  
Henry F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Aortic Valve ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
No Reduction ◽  
Rabbit Model ◽  
Daily Regimen ◽  
Methicillin Resistant ◽  
Days Of Therapy ◽  
Time Kill

ABSTRACT The activities of telavancin and vancomycin were compared in vitro and in the rabbit model of aortic valve endocarditis against a methicillin-resistant Staphylococcus aureus strain, COL, and a vancomycin-intermediate S. aureus (VISA) strain, HIP 5836. Telavancin was bactericidal in time-kill studies at a concentration of 5 μg/ml against both COL and HIP5836. Vancomycin was bacteriostatic at 5 μg/ml and bactericidal at 10 μg/ml against COL and was bacteriostatic at 10 μg/ml against VISA strain HIP 5836. Compared to untreated controls, a twice-daily regimen of 30 mg/kg of telavancin reduced mean aortic valve vegetation titers of the COL strain by 4.7 log10 CFU/g after 4 days of therapy and sterilized 6/11 vegetations compared to 3.4 log10 CFU/g with 3/10 vegetations sterilized for a regimen of twice-daily vancomycin, 30 mg/kg; these differences were not statistically significant. Telavancin was significantly more effective than vancomycin in the VISA model, producing a 5.5 log10 CFU/g reduction versus no reduction in CFU with vancomycin. In experiments comparing 2-day regimens of telavancin at 30 mg/kg and 50 mg/kg twice daily, organisms were rapidly eliminated from vegetations, but the effect was not different between the two doses. These results suggest that telavancin may be an effective treatment for endocarditis and other serious staphylococcal infections accompanied by bacteremia, including infections caused by staphylococci not susceptible to vancomycin.

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

scholarly journals Efficacy of LY333328 against Experimental Methicillin-Resistant Staphylococcus aureus Endocarditis

1998 ◽  
Vol 42 (4) ◽  
pp. 981-983 ◽  
Author(s):  
Glenn W. Kaatz ◽  
Susan M. Seo ◽  
Jeffrey R. Aeschlimann ◽  
Heather H. Houlihan ◽  
Renee-Claude Mercier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Rabbit Model ◽  
Glycopeptide Antibiotic ◽  
In Vivo Efficacy ◽  
Methicillin Resistant ◽  
Therapeutic Alternative ◽  
Staphylococcus Aureus Endocarditis

ABSTRACT The in vivo efficacy of LY333328, a new glycopeptide antibiotic, was compared with that of vancomycin by using the rabbit model of left-sided methicillin-resistant Staphylococcus aureusendocarditis. Animals received LY333328 or vancomycin (25 mg/kg of body weight every 24 or 8 h, respectively) for 4 days. These drugs were equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and tissues. We conclude that in this model, LY333328 was microbiologically effective and may be a therapeutic alternative to vancomycin.

Sign in / Sign up

Export Citation Format

Share Document