Association Between β-Lactam Exposure and Clearance of Bacteremia and Acute Kidney Injury in Patients with Methicillin-Resistant Staphylococcus aureus Bloodstream Infections – a Post Hoc Analysis of the CAMERA2 Trial

AbstractObjectives In the CAMERA2 trial, combination of vancomycin and seven days of a β-lactam resulted in faster clearance of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and higher rates of nephrotoxicity compared to monotherapy. Many participants received empirical β-lactam prior to enrolment. Whether the duration of β-lactam use, including the empiric treatment, impacts clinical and microbiological outcomes is unclear. Methods In a post-hoc analysis of the CAMERA2 study, we investigated the impact of β-lactam therapy duration on the hazard ratio (HR) for clearance of bacteremia and the odds ratio (OR) for development of acute kidney injury (AKI). β-lactam use was categorised as ‘Early' (any β-lactam for ≥24 hours from time of blood culture collection until trial randomization), ‘Late' (flucloxacillin or cefazolin for 7 days, only post-randomization), ‘Throughout' (Early + Late) or ‘None' (Results Compared to no β-lactam treatment (n=74), ‘Early' (n=104), ‘Late' (n=63) or ‘Throughout' (n=111) β-lactam receipt was associated with adjusted HRs (95% confidence interval) for faster clearance of bacteremia of 1.59(1.16-2.19), 1.62(1.14-2.31) and 1.85(1.36-2.52) respectively. Compared to ‘None' (n=61), ‘Early' (n=81), ‘Late' (n=52) and ‘Throughout' (n=92) groups had adjusted ORs of AKI of 1.24(0.27-6.60), 6.01(1.61-29.60) and 7.93(2.43-36.30) respectively. Conclusions Combination treatment with a β-lactam was associated with a duration-dependent effect on clearance of bacteremia and AKI. Short-duration antistaphylococcal β-lactam during the empiric treatment period was associated with faster clearance of MRSA bacteremia, and may not substantially increase the risk of nephrotoxicity.