LAUSR

Vancomycin, administered by continuous infusion, (VCI) is used to treat serious gram positive infections in outpatients. We retrospectively investigated the rate of nephrotoxicity and associated risk factors in outpatients on VCI between May 2013 and November 2018. The patients had twice weekly vancomycin concentration monitoring to ensure adequate concentrations while avoiding high concentrations linked to nephrotoxicity. The likelihood of developing nephrotoxicity (a rise in serum creatinine of ≥ 50% or 44 µmol/L from baseline) was evaluated using multivariable logistic regression. The 223 adult patients treated had a mean (standard deviation) age of 61 (16.7) years, baseline serum creatinine of 83.9 (21.2) µmol/L and estimated glomerular filtration rate of 80.6 (20.1) mL/min/1.73m2. Most (66%) were treated for bone and joint infections. Eight patients (3.4%) developed nephrotoxicity. In the most parsimonious model, nephrotoxicity was independently associated with an increased median (interquartile range) weighted average serum vancomycin concentration [28.0 (24.3 - 32.6) versus 22.4 (20.2 - 24.5) mg/L; OR 1.25; 95% CI 1.09 - 1.45; p < 0.002] and Charlson co-morbidity index (OR 1.66; 95% CI 1.07 - 2.45; p=0.02). Post-hoc analysis identified 26 patients with a lower nephrotoxicity threshold (rise in serum creatinine of ≥ 30% or 27 mmol/L). Independent predictors of nephrotoxicity in this group were an increased weighted average vancomycin concentration, diabetes, congestive heart failure and exposure to non-loop diuretics. Our nephrotoxicity rate during VCI was lower than previously reported (3.4% versus 15.0 - 17.0%).  Reducing the weighted average serum vancomycin concentration may reduce nephrotoxicity while maintaining efficacy.