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bioRxiv · 10.1101/2021.03.12.435219

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

Huang, D.·Gaukel, E.·Kerzee, N.·Borroto-Esoda, K.·Lowry, S.·Xiong, Y. Q.·Abdelhady, W.·Bayer, A.
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Abstract

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.

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Huang, D., Gaukel, E., Kerzee, N., Borroto-Esoda, K., Lowry, S., Xiong, Y. Q., Abdelhady, W., Bayer, A.. 2021-03-14. Efficacy of Anti-Staphylococcal Lysin, LSVT-1701, in Combination with Daptomycin in Experimental Left-Sided Infective Endocarditis Due to Methicillin-Resistant Staphylococcus aureus (MRSA). https://doi.org/10.1101/2021.03.12.435219

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