Risk Factors for Nephrotoxicity in Methicillin-Resistant Staphylococcus aureus Bacteraemia: A Post Hoc Analysis of the CAMERA2 Trial.


Journal

Clinical drug investigation
ISSN: 1179-1918
Titre abrégé: Clin Drug Investig
Pays: New Zealand
ID NLM: 9504817

Informations de publication

Date de publication:
Jan 2023
Historique:
accepted: 13 09 2022
pubmed: 11 10 2022
medline: 14 1 2023
entrez: 10 10 2022
Statut: ppublish

Résumé

Clinical risk factors for nephrotoxicity in Staphylococcus aureus bacteraemia remain largely undetermined, despite its common occurrence and clinical significance. In an international, multicentre, prospective clinical trial (CAMERA2), which compared standard therapy (vancomycin monotherapy) to combination therapy (adding an anti-staphylococcal beta-lactam) for methicillin-resistant S. aureus bacteraemia, significantly more people in the combination therapy arm experienced acute kidney injury compared with those in the monotherapy arm (23% vs 6%). The aim of this post hoc analysis was to explore in greater depth the risk factors for acute kidney injury from the CAMERA2 trial. Among participants of the CAMERA2 trial, demographic-related, infection-related and treatment-related risk factors were assessed for their relationship with acute kidney injury by univariable and multivariable logistic regression. Acute kidney injury was defined by a modified-KDIGO (Kidney Disease: Improving Global Outcomes) criteria (not including urinary output). Of the 266 participants included, age (p = 0.04), randomisation to combination therapy (p = 0.002), vancomycin area under the concentration-time curve (p = 0.03) and receipt of (flu)cloxacillin as the companion beta-lactam (p < 0.001) were significantly associated with acute kidney injury. On a multivariable analysis, concurrent use of (flu)cloxacillin increased the risk of acute kidney injury over four times compared with the use of cefazolin or no beta-lactam. The association of vancomycin area under the concentration-time curve with acute kidney injury also persisted in the multivariable model. For participants receiving vancomycin for S. aureus bacteraemia, use of (flu)cloxacillin and increased vancomycin area under the concentration-time curve were risk factors for acute kidney injury. These represent potentially modifiable risk factors for nephrotoxicity and highlight the importance of avoiding the use of concurrent nephrotoxins.

Sections du résumé

BACKGROUND BACKGROUND
Clinical risk factors for nephrotoxicity in Staphylococcus aureus bacteraemia remain largely undetermined, despite its common occurrence and clinical significance. In an international, multicentre, prospective clinical trial (CAMERA2), which compared standard therapy (vancomycin monotherapy) to combination therapy (adding an anti-staphylococcal beta-lactam) for methicillin-resistant S. aureus bacteraemia, significantly more people in the combination therapy arm experienced acute kidney injury compared with those in the monotherapy arm (23% vs 6%).
OBJECTIVE OBJECTIVE
The aim of this post hoc analysis was to explore in greater depth the risk factors for acute kidney injury from the CAMERA2 trial.
METHODS METHODS
Among participants of the CAMERA2 trial, demographic-related, infection-related and treatment-related risk factors were assessed for their relationship with acute kidney injury by univariable and multivariable logistic regression. Acute kidney injury was defined by a modified-KDIGO (Kidney Disease: Improving Global Outcomes) criteria (not including urinary output).
RESULTS RESULTS
Of the 266 participants included, age (p = 0.04), randomisation to combination therapy (p = 0.002), vancomycin area under the concentration-time curve (p = 0.03) and receipt of (flu)cloxacillin as the companion beta-lactam (p < 0.001) were significantly associated with acute kidney injury. On a multivariable analysis, concurrent use of (flu)cloxacillin increased the risk of acute kidney injury over four times compared with the use of cefazolin or no beta-lactam. The association of vancomycin area under the concentration-time curve with acute kidney injury also persisted in the multivariable model.
CONCLUSIONS CONCLUSIONS
For participants receiving vancomycin for S. aureus bacteraemia, use of (flu)cloxacillin and increased vancomycin area under the concentration-time curve were risk factors for acute kidney injury. These represent potentially modifiable risk factors for nephrotoxicity and highlight the importance of avoiding the use of concurrent nephrotoxins.

Identifiants

pubmed: 36217068
doi: 10.1007/s40261-022-01204-z
pii: 10.1007/s40261-022-01204-z
pmc: PMC9834357
doi:

Substances chimiques

Anti-Bacterial Agents 0
beta-Lactams 0
Cefazolin IHS69L0Y4T
Cloxacillin O6X5QGC2VB
Vancomycin 6Q205EH1VU

Types de publication

Clinical Trial Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

23-33

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2022. Crown.

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Auteurs

Amy Legg (A)

Menzies School of Health Research, Darwin, NT, Australia. amy.legg@health.qld.gov.au.

Niamh Meagher (N)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
Department of Infectious Diseases at The Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia.

Sandra A Johnson (SA)

Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Matthew A Roberts (MA)

Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia.

Alan Cass (A)

Menzies School of Health Research, Darwin, NT, Australia.

Marc H Scheetz (MH)

Department of Pharmacy Practice, Midwestern University Chicago College of Pharmacy, Downers Grove, IL, USA.
Department of Pharmacology, Midwestern University College of Graduate Studies, Downers Grove, IL, USA.
Pharmacometrics Center of Excellence, Midwestern University, Downers Grove, IL, USA.
Department of Pharmacy, Northwestern Medicine, Chicago, IL, USA.

Jane Davies (J)

Menzies School of Health Research, Darwin, NT, Australia.
Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT, Australia.

Jason A Roberts (JA)

Faculty of Medicine, University of Queensland Centre for Clinical Research (UQCCR), Brisbane, QLD, Australia.
Departments of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.

Joshua S Davis (JS)

Menzies School of Health Research, Darwin, NT, Australia.
School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia.

Steven Y C Tong (SYC)

Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Department of Infectious Diseases, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

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