Longer-term Mortality and Kidney Outcomes of Participants in the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial: A Post Hoc Analysis
Authors: Legg Amy , Roberts Matthew A , Davies Jane , Cass Alan , Meagher Niamh , Sud Archana , Daitch Vered , Dishon Benattar Yael , Yahav Dafna , Paul Mical , Xinxin Chen , Ping Yeo He , Lye David , Lee Russel , Robinson J Owen , Foo Hong , Tramontana Adrian R , Bak Narin , Grenfell Adelaide , Rogers Benjamin , Li Ying , Joshi Neela , O’Sullivan Matthew , McKew Genevieve , Ghosh Niladri , Schneider Kellie , Holmes Natasha E , Dotel Ravindra , Chia Timothy , Archuleta Sophia , Smith Simon , Warner Morgyn S , Titin Christina , Kalimuddin Shirin , Roberts Jason A , Tong Steven Y C , Davis Joshua S ,   for the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Study Group, Tong Steven Y C , Lye David C , Yahav Dafna , Sud Archana , Robinson J Owen , Nelson Jane , Archuleta Sophia , Roberts Matthew A , Cass Alan , Paterson David L , Foo Hong , Paul Mical , Guy Stephen D , Tramontana Adrian R , Walls Genevieve B , McBride Stephen , Bak Narin , Ghosh Niladri , Rogers Benjamin A , Ralph Anna P , Davies Jane , Ferguson Patricia E , Dotel Ravindra , McKew Genevieve L , Gray Timothy J , Holmes Natasha E , Smith Simon , Warner Morgyn S , Kalimuddin Shirin , Young Barnaby E , Runnegar Naomi , Andresen David N , Anagnostou Nicholas A , Johnson Sandra A , Chatfield Mark D , Cheng Allen C , Fowler Vance G , Howden Benjamin P , Meagher Niamh , Price David J , van Hal Sebastiaan J , Gill Satinder , Rofe Alexander , O'Sullivan Matthew , Davis Joshua S 
Published: June 2023

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 &lt;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.