Association between β-lactam exposure and clearance of bacteraemia and acute kidney injury in patients with methicillin-resistant Staphylococcus aureus bloodstream infections—a post hoc analysis of the CAMERA2 trial

OBJECTIVES: In the Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial, combination of vancomycin and 7 days of a β-lactam resulted in faster clearance of methicillin-resistant Staphylococcus aureus bacteraemia and higher rates of nephrotoxicity compared with 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 for clearance of bacteraemia and the odds ratio (OR) for development of acute kidney injury (AKI). β-Lactam use was categorized as 'Early' (any β-lactam for ≥24 hours from time of blood culture collection until trial randomization), 'Late' ([flu]cloxacillin or cefazolin for 7 days, only after randomization), 'Throughout' (Early + Late) or 'None' (<24 hours of any β-lactam). Participants requiring renal replacement therapy at baseline were excluded from assessment of AKI. RESULTS: Compared with no β-lactam treatment (n = 74), 'Early' (n = 104), 'Late' (n = 63) or 'Throughout' (n = 111) β-lactam receipt was associated with adjusted hazard ratios (95% CI) for faster clearance of bacteraemia of 1.59 (1.16-2.19), 1.62 (1.14-2.31) and 1.85 (1.36-2.52), respectively. Compared with '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 bacteraemia and AKI. Short-duration antistaphylococcal β-lactam during the empiric treatment period was associated with faster clearance of methicillin-resistant S. aureus bacteraemia, and may not substantially increase the risk of nephrotoxicity.