Ability of Bicarbonate Supplementation to Sensitize Selected Methicillin-Resistant Staphylococcus aureus (MRSA) Strains to β-Lactam Antibiotics in an Ex Vivo Simulated Endocardial Vegetation Model.

Ability of Bicarbonate Supplementation to Sensitize Selected Methicillin-Resistant Staphylococcus aureus (MRSA) Strains to β-Lactam Antibiotics in an Ex Vivo Simulated Endocardial Vegetation Model. Antimicrob Agents Chemother. 2019 Dec 16;: Authors: Rose WE, Bienvenida AM, Xiong YQ, Chambers HF, Bayer AS, Ersoy SC Abstract Supplementation of standard growth media (cation-adjusted Mueller-Hinton Broth [CAMHB]) with bicarbonate (NaHCO3 ) increases β-lactam susceptibility of selected MRSA strains ("NaHCO3-responsive"). This "sensitization" phenomenon translated to enhanced β-lactam efficacy in a rabbit model of endocarditis. The present study evaluated NaHCO3-mediated β-lactam MRSA sensitization using an ex vivo pharmacodynamic model, featuring simulated endocardial vegetations (SEVs), to more closely mimic the host microenvironment. Four previously-described MRSA were used: two each exhibiting in vitro NaHCO3-responsive or NaHCO3-nonresponsive phenotypes. Cefazolin (CFZ) and oxacillin (OXA) were evaluated in CAMHB±NaHCO3 Intra-SEV MRSA killing was determined over 72 hr exposures. In both "responsive" strains, supplementation with 25 mM or 44 mM NaHCO3 significantly reduced β-lactam MICs to below the OXA susceptibility breakpoint (≤ 4 mg/L) and resulted in bactericidal activity (≥ 3 log kill) in the model for both OXA and CFZ. In contrast, neither in vitro-defined non-responsive MRSA strains showed significant sensitization in...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research