607. Scope and Predictive Genetic/Phenotypic Signatures of “Bicarbonate [NaHCO3]-Responsivity” and β-Lactam Sensitization among Methicillin-Resistant Staphylococcus aureus (MRSA)

Abstract

BackgroundSelected MRSA strains become susceptible to β-lactams (e.g., oxacillin [OX]; cefazolin [CFZ]) in vitro when tested in a standard medium (cation-adjusted Mueller–Hinton Broth; CA-MHB) supplemented with NaHCO3 (“NaHCO3-responsivity”). In vivo activity of β-lactams was demonstrated for MRSA strains with this phenotype in a rabbit endocarditis model (Ersoy et al Antimicrob Agents Chemother 2019). The current study was designed to: (i) determine the prevalence of the NaHCO3-responsive phenotype in a large collection of clinical MRSA isolates; and (ii) identify genetic and phenotypic predictors of this phenotype. Methods. 58 recent MRSA bloodstream isolates representing contemporary clonal complex (CC) genotypes were screened for the NaHCO3-responsive phenotype by broth microdilution MICs in CA-MHB, with or without NaHCO3 supplementation (25–44 mM).Methods58 recent MRSA bloodstream isolates representing contemporary clonal complex (CC) genotypes were screened for the NaHCO3-responsive phenotype by broth microdilution MICs in CA-MHB, with or without NaHCO3 supplementation (25–44 mM).Results43/58 (74.1%) and 21/58 (36.2%) were rendered susceptible to CFZ and OX, respectively, in the presence of NaHCO3; 20 of the 21 OX-susceptible strains were also susceptible to CFZ in the presence of NaHCO3. High baseline β-lactam MICs (i.e., MICs in CA-MHB alone ≥64 µg/mL) was not predictive of NaHCO3 responsivity. The CC8 genotype was correlated with NaHCO3 responsivity for OX, but not CFZ (P < 0.05).ConclusionThe NaHCO3-responsive phenotype is relatively common for both OX and especially CFZ among clinical MRSA isolates. Identification of specific genetic factors linked to this phenotype remains ongoing. Confirmation in relevant animal models that this phenotype is predictive of β-lactam efficacy in vivo could provide a solid foundation for a paradigm shift in antimicrobial susceptibility testing of MRSA.Disclosures All authors: No reported disclosures.