{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T03:41:34Z","timestamp":1783395694651,"version":"3.54.6"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["1RO1AI146078"],"award-info":[{"award-number":["1RO1AI146078"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"MOH | National Medical Research Council","award":["0001-001094"],"award-info":[{"award-number":["0001-001094"]}]},{"name":"DHAC | National Health and Medical Research Council","award":["1078930"],"award-info":[{"award-number":["1078930"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,7,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              NaHCO\n              <jats:sub>3<\/jats:sub>\n              responsiveness is a novel phenotype where some methicillin-resistant\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and\/or cefazolin in the presence of NaHCO\n              <jats:sub>3<\/jats:sub>\n              . NaHCO\n              <jats:sub>3<\/jats:sub>\n              responsiveness correlated with treatment response to \u03b2-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive strains with \u03b2-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              ) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal \u03b2-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\n              <jats:sub>3<\/jats:sub>\n              . Isolates exhibiting \u22654-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO\n              <jats:sub>3<\/jats:sub>\n              were considered \u201cNaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive\u201d to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive and non-responsive strains, and that were assigned to combination treatment with a \u03b2-lactam. Thirty-one percent (36\/117) and 25% (21\/85) of MRSA isolates were NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive to cefazolin and oxacillin, respectively. The NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive phenotype was significantly associated with sequence type 93, SCC\n              <jats:italic>mec<\/jats:italic>\n              type IVa, and\n              <jats:italic>mecA<\/jats:italic>\n              alleles with substitutions in positions \u22127 and \u221238 in the regulatory region. Among participants treated with a \u03b2-lactam, there was no association between the NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive phenotype and persistent bacteremia (cefazolin,\n              <jats:italic>P<\/jats:italic>\n              = 0.82; oxacillin,\n              <jats:italic>P<\/jats:italic>\n              = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an\n              <jats:italic>in vitro<\/jats:italic>\n              \u03b2-lactam-NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a \u03b2-lactam.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00218-24","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T17:12:33Z","timestamp":1717607553000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Genomic investigation and clinical correlates of the\n            <i>in vitro<\/i>\n            \u03b2-lactam: NaHCO\n            <sub>3<\/sub>\n            responsiveness phenotype among methicillin-resistant\n            <i>Staphylococcus aureus<\/i>\n            isolates from a randomized clinical trial"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1981-3848","authenticated-orcid":true,"given":"Neta","family":"Petersiel","sequence":"first","affiliation":[{"name":"Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"},{"name":"Department of Infectious Diseases, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-1943","authenticated-orcid":false,"given":"Stefano","family":"Giulieri","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Service, The Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"},{"name":"Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane S.","family":"Daniel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"},{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sook-Ha","family":"Fan","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-2061","authenticated-orcid":false,"given":"Selvi C.","family":"Ersoy","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-5699","authenticated-orcid":false,"given":"Joshua S.","family":"Davis","sequence":"additional","affiliation":[{"name":"Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia"},{"name":"Department of Infectious Diseases, John Hunter Hospital, Newcastle, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold S.","family":"Bayer","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, California, USA"},{"name":"The Geffen School of Medicine, University of California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin P.","family":"Howden","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"},{"name":"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"},{"name":"Centre for Pathogen Genomics, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-8356","authenticated-orcid":false,"given":"Steven Y. 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