Scope and Predictive Genetic/Phenotypic Signatures of Bicarbonate (NaHCO3) Responsiveness and β-Lactam Sensitization in Methicillin-Resistant Staphylococcus aureus.

Selvi C Ersoy,Yan Q Xiong,Arnold S Bayer,Vance G Fowler,Mariam Otmishi,Vanessa T Milan,Liang Chen,Henry F Chambers,Jose Mediavilla,Liang Li,Barry Kreiswirth,Youngju Pak,Richard A Proctor

doi:10.1128/aac.02445-19

Abstract

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA.

Highlights

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to ␤-lactams
Staphylococcus aureus is a serious community and nosocomial pathogen and a leading cause of bacteremia, infective endocarditis, and device-related infections [1, 2]. Many of these infections are caused by methicillin-resistant S. aureus (MRSA), which is generally perceived to be “resistant” to those ␤-lactam antibiotic therapies used for the treatment of methicillin-susceptible S. aureus (MSSA) [3]
MRSA exhibits in vitro resistance to oxacillin (OXA) by standard antimicrobial susceptibility testing (AST), which has been extrapolated to apply to all other ␤-lactams [4]

Summary

Introduction

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to ␤-lactams. We identified a novel MRSA AST phenotype, termed “NaHCO3 responsiveness,” in which MRSA strains are highly susceptible in vitro to cefazolin (CFZ) and OXA in a medium supplemented with NaHCO3 [7]. We identified a relatively large subset of NaHCO3-responsive strains to CFZ and/or OXA within this MRSA cohort.

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Results

Conclusion