Legg A

Meagher N

Johnson SA

Roberts MA

Cass A

Scheetz MH

Davies, Jane

Roberts JA

Davis JS

Tong SYC

2022-10-10

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: 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: 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: 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: 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.

UQCCR, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia. amy.legg@health.qld.gov.au.

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.

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

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

UQCCR, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia.

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.

Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT, Australia.

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.

School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia.

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.

Clin Drug Investig . 2023 Jan;43(1):23-33. doi: 10.1007/s40261-022-01204-z. Epub 2022 Oct 10.

0000-0001-8228-1536

0000-0001-6218-435X

https://pubmed.ncbi.nlm.nih.gov/36217068/?otool=iaurydwlib

https://hdl.handle.net/10137/12312

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

Journal Article

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