Genomic investigation and clinical correlates of the in vitro β-lactam: NaHCO 3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.

Autor:	Petersiel N; 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., Giulieri S; 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., Daniel DS; 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., Fan S-H; The Lundquist Institute for Biomedical Innovation, Torrance, California, USA., Ersoy SC; The Lundquist Institute for Biomedical Innovation, Torrance, California, USA., Davis JS; 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., Bayer AS; The Lundquist Institute for Biomedical Innovation, Torrance, California, USA.; The Geffen School of Medicine, University of California, Los Angeles, California, USA., Howden BP; 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.; Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia., Tong SYC; 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.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2024 Jul 09; Vol. 68 (7), pp. e0021824. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1128/aac.00218-24
Abstrakt:	NaHCO 3 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 NaHCO 3 . NaHCO 3 responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO 3 -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 NaHCO 3 . Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO 3 were considered "NaHCO 3 -responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO 3 -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 NaHCO 3 -responsive to cefazolin and oxacillin, respectively. The NaHCO 3 -responsive phenotype was significantly associated with sequence type 93, SCC mec 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 NaHCO 3 -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-NaHCO 3 -responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a β-lactam. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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