Impact of a kidney-sparing protocol for the treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections (CLOXECO): a quasi-experimental study

Background: Antistaphylococcal penicillin (ASP) is the first-line therapy for MSSA bloodstream infection (BSI), with cefazolin as an alternative. However, ASPs are associated with a high risk of acute kidney injury (AKI) and overexposure. We implemented a kidney-sparing protocol based on: (i) systematic use of cefazolin in patients with creatinine clearance of <60 mL/min or any risk factor for AKI; and (ii) reduced ASP dose (75-100 mg/kg/day) with therapeutic drug monitoring. Methods: We compared all episodes of MSSA BSI in adults admitted during the 15 months before (control period) and the 12 months after (optimization period) protocol implementation. Primary outcome was sterile blood cultures by Day 3. Secondary outcomes included AKI, dialysis, MSSA BSI relapses, and mortality. Results: We included 100 patients in the control group and 104 in the optimization group. Baseline characteristics were similar in both groups, with a mean +/- SD age of 73 +/- 20 years, male predominance (73%), and high prevalence of chronic kidney disease (80%) and diabetes (31%). Initial treatment was ASP (cloxacillin) in 80/100 (80%) patients in the control group, versus 24/104 (23%) in the optimization group (P < 0.001). Day 3 sterile blood cultures, and Day 30 mortality remained similar (respectively 95% versus 93%, and 21% versus 24%; not significant). AKI and dialysis requirements were less frequent during the optimization period, respectively 37% versus 56% (P = 0.045), and 1% versus 8% (P = 0.017). Conclusions: A kidney-sparing protocol for MSSA BSI based on systematic use of cefazolin in patients with AKI risk factor, and lower ASP doses, was associated with similar efficacy and lower risk of AKI and dialysis requirements.