Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/35335
Title: Genomic investigation and clinical correlates of the in vitro β-lactam: NaHCO3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.
Austin Authors: Petersiel, Neta;Giulieri, Stefano G ;Daniel, Diane S;Fan, Sook-Ha;Ersoy, Selvi C;Davis, Joshua S;Bayer, Arnold S;Howden, Benjamin P ;Tong, Steven Y C
Affiliation: Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.;Department of Infectious Diseases, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.;Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.;Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
The Lundquist Institute for Biomedical Innovation, Torrance, California, USA.
Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.;Department of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia.
The Lundquist Institute for Biomedical Innovation, Torrance, California, USA.;The Geffen School of Medicine, University of California, Los Angeles, California, USA.
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.;Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.;Centre for Pathogen Genomics, The University of Melbourne, Melbourne, Victoria, Australia.
Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.;Department of Infectious Diseases, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Infectious Diseases
Issue Date: 5-Jun-2024
Date: 2024
Publication information: Antimicrobial Agents and Chemotherapy 2024-06-05
Abstract: NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with β-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered "NaHCO3-responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a β-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a β-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro β-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a β-lactam.
URI: https://ahro.austin.org.au/austinjspui/handle/1/35335
DOI: 10.1128/aac.00218-24
ORCID: 0000-0003-1981-3848
0000-0001-5366-1943
0000-0002-8792-2061
0000-0001-9864-5699
0000-0002-1368-8356
Journal: Antimicrobial Agents and Chemotherapy
Start page: e0021824
PubMed URL: 38837393
ISSN: 1098-6596
Type: Journal Article
Subjects: MRSA
bacterial genomics
bloodstream-infections
methicillin-resistant Staphylococcus aureus
sodium bicarbonate (NaHCO3)
β-lactams
Appears in Collections:Journal articles

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