Longer-term mortality and kidney outcomes of participants in the combination antibiotics for methicillin-resistant Staphylococcus aureus (CAMERA2) trial: a post hoc analysis

• Main Authors: Legg, Amy, Roberts, Matthew A., Davies, Jane, Cass, Alan, Meagher, Niamh, Sud, Archana, Daitch, Vered, Dishon Benattar, Yael, Yahav, Dafna, Paul, Mical, Chen, Xinxin, Yeo, He Ping, Lye, David C., 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.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Medicine; Acute Kidney Injury; Nephrotoxicity
• Online Access: https://hdl.handle.net/10356/171771
• Institution: Nanyang Technological University

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.