Bicarbonate Resensitization of Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics.

Bicarbonate Resensitization of Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics. Antimicrob Agents Chemother. 2019 Apr 22;: Authors: Ersoy SC, Abdelhady W, Li L, Chambers HF, Xiong YQ, Bayer AS Abstract Endovascular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major healthcare concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as 'resistant' to β-lactams, often leading to use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. We identified two distinct MRSA phenotypes upon AST using standard media, with or without sodium bicarbonate (NaHCO3 ) supplementation: one highly susceptible to the anti-staphylococcal β-lactams, oxacillin and cefazolin ('NaHCO3-responsive') and one resistant to such agents ('NaHCO3-nonresponsive'). These phenotypes accurately predicted clearance profiles of MRSA from target tissues in experimental MRSA IE treated with each β-lactam. Mechanistically, NaHCO3 reduced expression of two key genes involved in the MRSA phenotype, mecA and sarA, leading to decreased production of penicillin-binding protein (PBP) 2a (that mediates methicillin resistance), in NaHCO3-responsive (but not in NaHCO3-nonresponsive) strains. Moreover, both cefazolin and oxacillin synergis...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research