Accès ouvert déclaré 2024 article

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

Neta Petersiel, Stefano G. Giulieri, Diane S. Daniel, Sook‐Ha Fan, Selvi C. Ersoy, Joshua Saul Davis, Arnold S. Bayer, Benjamin P. Howden, Steven Y. C. Tong, David Chien Lye, Dafna Yahav, Archana Sud, James Owen Robinson, Jane Nelson, Sophia Archuleta, Matthew A. Roberts, Alan Cass, David L. Paterson, Hong Foo, Mical Paul, Stephen Guy, Adrian R Tramontana, Genevieve B. Walls, Stephen McBride, Narin Bak, Niladri Ghosh, Benjamin A. Rogers, Anna P. Ralph, Jane Davies, Patricia E. Ferguson, Ravindra Dotel, Genevieve L. McKew, Timothy James Gray, Natasha E. Holmes, Simon Smith, Morgyn S. Warner, Shirin Kalimuddin, Barnaby Edward Young, David N. Andresen, Nicholas A. Anagnostou, Sandra A. S. Johnson, Mark D. Chatfield, ALLEN C. CHENG, Vance G. Fowler, Niamh Meagher, David J. Price, Sebastiaan J. van Hal, Matthew V. N. O'Sullivan

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Le résumé fourni par la source

ABSTRACT 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.

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Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.

Titre Crossref: 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
Date Crossref: 09/07/2024
Éditeur: American Society for Microbiology
Type: journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Où se fait cette recherche

The Royal Melbourne Hospital Victorian Infectious Diseases Service pays non établi dans la notice
Organisme public
The University of Melbourne Department of Infectious Diseases pays non établi dans la notice
Université ou école supérieure
Peter Doherty Institute pays non établi dans la notice
Structure de recherche
John Hunter Hospital Department of Infectious Diseases pays non établi dans la notice
Établissement de santé
Charles Darwin University pays non établi dans la notice
Université ou école supérieure
Menzies School of Health Research pays non établi dans la notice
Organisation à but non lucratif
University of California pays non établi dans la notice
Université ou école supérieure
Austin Health pays non établi dans la notice
Établissement de santé
The Lundquist Institute for Biomedical Innovation pays non établi dans la notice
Structure de recherche
The Geffen School of Medicine pays non établi dans la notice
Université ou école supérieure
Department of Infectious Diseases pays non établi dans la notice
Institution

Victorian Infectious Diseases Service — The Royal Melbourne Hospital, Department of Infectious Diseases — The University of Melbourne et Peter Doherty Institute, avec 8 autres affiliations.

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Antimicrobial Resistance in StaphylococcusAntibiotics Pharmacokinetics and EfficacyInfective Endocarditis Diagnosis and Management

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