@article{d86af174c8f84941b0757af4f6c7d313,
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",
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.",
keywords = "MRSA, bacterial genomics, bloodstream-infections, methicillin-resistant Staphylococcus aureus, sodium bicarbonate (NaHCO), β-lactams",
author = "{CAMERA2 study group} and Neta Petersiel and Stefano Giulieri and Daniel, {Diane S.} and Fan, {Sook Ha} and Ersoy, {Selvi C.} and Davis, {Joshua S.} and Bayer, {Arnold S.} and Howden, {Benjamin P.} and Tong, {Steven Y.C.} and Lye, {David C.} and Dafna Yahav and Archana Sud and Robinson, {J. Owen} and Jane Nelson and Sophia Archuleta and Roberts, {Matthew A.} and Alan Cass and Paterson, {David L.} and Hong Foo and Mical Paul and Guy, {Stephen D.} and Tramontana, {Adrian R.} and Walls, {Genevieve B.} and Stephen McBride and Narin Bak and Niladri Ghosh and Rogers, {Benjamin A.} and Ralph, {Anna P.} and Jane Davies and Ferguson, {Patricia E.} and Ravindra Dotel and McKew, {Genevieve L.} and Gray, {Timothy J.} and Holmes, {Natasha E.} and Simon Smith and Warner, {Morgyn S.} and Shirin Kalimuddin and Young, {Barnaby E.} and Naomi Runnegar and Andresen, {David N.} and Anagnostou, {Nicholas A.} and Johnson, {Sandra A.} and Chatfield, {Mark D.} and Cheng, {Allen C.} and Fowler, {Vance G.} and Howden, {Benjamin P.} and Niamh Meagher and Price, {David J.} and {van Hal}, {Sebastiaan J.} and O'Sullivan, {Matthew V.N.}",
note = "Publisher Copyright: {\textcopyright} 2024 American Society for Microbiology. All Rights Reserved.",
year = "2024",
month = jul,
doi = "10.1128/aac.00218-24",
language = "אנגלית",
volume = "68",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "7",
}
