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

Abstract

Background The Combination Antibiotic therapy for MEthicillin Resistant Staphylococcus Aureus (CAMERA2) trial ceased recruitment in July 2018, noting a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analysed 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 renal failure or a reduction in kidney function (a 40% reduction in eGFR to less than 60 mL/min/1.73m2). 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 randomisation; 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 0.83 [95% CI 0.59–1.19], p = 0.33) or experiencing an AKI (hazard ratio at one year 1.04 [95% CI 0.64–1.68], p = 0.88). Conclusion In this cohort of patients hospitalised with MRSA bacteraemia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.