Vancomycin-associated nephrotoxicity in non-critically ill patients admitted in a Brazilian public hospital: A prospective cohort study

INTRODUCTION: Vancomycin is widely used to treat infections caused by Gram positive bacteria, mostly methicillin-resistant strains. Despite its therapeutic effectiveness, vancomycin is a nephrotoxic drug that has been associated with the occurrence of acute kidney injury (AKI). In this study, we sought to evaluate the variability of serum trough concentrations of vancomycin and to determine the incidence and risk factors of vancomycin-associated nephrotoxicity (VAN) in non-critically ill patients. METHODS: This was a prospective cohort including Brazilian public hospital inpatients from April 2017 to June 2018. The participants received intravenous vancomycin therapy for at least 48 hours for any suspected or confirmed infection by Gram positive bacteria. Demographic, clinical and laboratory data were collected. Information on vancomycin therapy and concomitant use of other nephrotoxic drugs were also recorded. Patients were followed up until discontinuation of vancomycin treatment or death, whatever occurred first. The primary outcome was the occurrence of AKI. We performed a Poisson regression to determine risk factors for AKI. RESULTS: Overall, 98 participants were included in the study. Median age was 55.9 (interquartile range [IQR] 40.6–66.8) years and 58 (59.2%) were men. Most of them showed subtherapeutic (<10mg/L) or supratherapeutic (>20mg/L) trough levels of vancomycin; 42.9% and 15.3%, respectively. A total of 19 (19.4%) patients developed AKI. Poisson regression showed that male sex (odds ratio [OR] 2.90; confidence interval [CI] 95% 1.28–6.53; p = 0.011), concomitant use of piperacillin-tazobactam (OR 4.66; CI 95% 2.26–9.58; p <0.001) and vancomycin trough levels above 20mg/mL (OR 4.21; CI 95% 1.57–11.278; p = 0.004) were independently associated with AKI. CONCLUSIONS: Our study showed that usual doses of vancomycin did not reach recommended therapeutic serum trough levels of vancomycin in non-critically ill patients. Besides that, nephrotoxicity was common in this population, being associated with male sex, concomitant use of piperacillin-tazobactam and supra-therapeutic trough serum levels of vancomycin.