Archive for July 18, 2019

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

Antimicrob Agents Chemother. June 24, 2019 V.63 N.7  pii: e00496-19.

Ersoy SC1, Abdelhady W1, Li L1, Chambers HF2, Xiong YQ3,4, Bayer AS1,4.

1 Los Angeles Biomedical Research Institute, Torrance, California, USA.

2 Division of Infectious Diseases, Zuckerberg San Francisco General Department of Medicine, San Francisco School of Medicine, University of California, San Francisco, California, USA.

3 Los Angeles Biomedical Research Institute, Torrance, California, USA yxiong@ucla.edu .

4 Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

Abstract

Endovascular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a major health care concern, especially infective endocarditis (IE).

Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as “resistant” to β-lactams, often leading to the 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 antistaphylococcal 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 the expression of two key genes involved in the MRSA phenotype, mecA and sarA, leading to decreased production of penicillin-binding protein 2a (that mediates methicillin resistance), in NaHCO3-responsive (but not in NaHCO3-nonresponsive) strains.

Moreover, both cefazolin and oxacillin synergistically killed NaHCO3-responsive strains in the presence of the host defense antimicrobial peptide (LL-37) in NaHCO3-supplemented media.

These findings suggest that AST of MRSA strains in NaHCO3-containing media may potentially identify infections caused by NaHCO3-responsive strains that are appropriate for β-lactam therapy.

FULL TEXT

https://aac.asm.org/content/63/7/e00496-19.long

PDF

https://aac.asm.org/content/aac/63/7/e00496-19.full.pdf

July 18, 2019 at 8:59 am


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