Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis

Amy Legg, Matthew A. Roberts, Jane Davies, Alan Cass, Niamh Meagher, Archana Sud, Vered Daitch, Yael Dishon Benattar, Dafna Yahav, Mical Paul, Chen Xinxin, Yeo He Ping, David Lye, Russel Lee, J. Owen Robinson, Hong Foo, Adrian R. Tramontana, Narin Bak, Adelaide Grenfell, Benjamin RogersYing Li, Neela Joshi, Matthew O'Sullivan, Genevieve McKew, Niladri Ghosh, Kellie Schneider, Natasha E. Holmes, Ravindra Dotel, Timothy Chia, Sophia Archuleta, Simon Smith, Morgyn S. Warner, Christina Titin, Shirin Kalimuddin, Jason A. Roberts, Steven Y.C. Tong, Joshua S. Davis

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Abstract

Background: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. 

Methods: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. 

Results: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI],. 59-1.19]; P =. 33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI,. 64-1.68]; P =. 88). Conclusions: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.

Original languageEnglish
Article numberofad337
Pages (from-to)1-9
Number of pages9
JournalOpen Forum Infectious Diseases
Volume10
Issue number7
DOIs
Publication statusPublished - 1 Jul 2023

Bibliographical note

Funding Information:
Financial support. The CAMERA2 trial was supported by the Australian National Health and Medical Research Council (NHMRC) Career Development Fellowships for S. Y. C. T. (1145033) and J. S. D. (1160331). J. A. R. acknowledges funding from the NHMRC for a Centre of Research Excellence (APP2007007) and an Investigator Grant (APP2009736) as well as an Advancing Queensland Clinical Fellowship.

Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.

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