Empirical glycopeptide exposure and acute kidney injury during cloxacillin therapy in Staphylococcus aureus bacteremia

ABSTRACT We aimed to identify risk factors for the development of acute kidney injury (AKI) during treatment of Staphylococcus aureus bacteremia (SAB), with particular emphasis on the roles of cloxacillin and cefazolin, and the contribution of other antibiotics. We performed a retrospective, observational, single-center study of a prospective cohort of patients with SAB receiving cloxacillin or cefazolin as definitive therapy and with serum creatinine available at baseline and days 5, 10, and 15. The primary outcome was the highest AKI stage between days 5 and 15; the secondary outcome was 30 day mortality. Univariate and multivariate analyses were performed to identify independent predictors of outcomes. A total of 470 patients were included in the study, and 103 (21.9%) developed AKI during hospitalization. Independent predictors of AKI were age >64 years (adjusted odds ratio [aOR] 1.76; 95% CI 1.08–2.87), peripheral arterial disease (aOR 2.23; 95% CI 1.02–4.88), chronic kidney disease (aOR 3.77; 95% CI 2.07–6.89), need of mechanical ventilation (aOR 3.33; 95% CI 1.62–6.86), and cloxacillin as definitive treatment with prior glycopeptide exposure (aOR 3.45; 95% CI 1.74–6.84). AKI occurred in 42.6% (23/52) of patients receiving empirical glycopeptide followed by cloxacillin, compared with 21.0% (61/290) in those treated with cloxacillin without prior glycopeptide exposure. The development of AKI during admission was an independent predictor of 30 day mortality (aOR 3.50; 95% CI 1.88–6.52). The only modifiable factor associated with AKI was the use of cloxacillin as definitive therapy after prior exposure to glycopeptides. These data reinforce the need to consider non-nephrotoxic alternatives.