Determinants of vancomycin nephrotoxicity when administered to outpatients as a continuous 24-hour infusion

Int J Antimicrob Agents. 2020 Jun;55(6):105972. doi: 10.1016/j.ijantimicag.2020.105972. Epub 2020 Apr 13.

Abstract

Vancomycin continuous infusion (VCI) is used to treat serious Gram-positive infections in outpatients. This study was conducted to retrospectively investigate the rate of nephrotoxicity and associated risk factors in out-patients on VCI between May 2013 and November 2018. Vancomycin concentration was monitored twice-weekly to ensure adequate concentrations while avoiding high concentrations linked to nephrotoxicity (a rise in serum creatinine of ≥50% or 44 µmol/L from baseline). The likelihood of developing nephrotoxicity was evaluated using multivariable logistic regression. The 223 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 (eGFR) of 80.6 (20.1) mL/min/1.73m2. Most patients (66%) were treated for bone and joint infections. Eight patients (3.6%) 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] vs. 22.4 [20.2-24.5] mg/L; odds ratio [OR] 1.25; 95% confidence interval [95% CI] 1.09-1.46; P<0.002) and Charlson co-morbidity index (OR 1.62; 95% CI 1.07-2.47; P=0.02). Post-hoc analysis identified 26 patients with a lower nephrotoxicity threshold (rise in serum creatinine of ≥30% or 27 μmol/L). Independent predictors of nephrotoxicity in this group were an increased weighted-average vancomycin concentration, diabetes, con-gestive heart failure and exposure to non-loop diuretics. The nephrotoxicity rate during VCI in this study was lower than previously reported (3.6% vs 15.0-17.0%). Reducing the weighted-average serum vancomycin concentration may reduce nephrotoxicity while maintaining efficacy.

Keywords: Drug monitoring; Home infusion therapy; Nephrotoxicity; Vancomycin.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects*
  • Biomarkers, Pharmacological
  • Creatinine / blood
  • Drug Monitoring
  • Female
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacterial Infections / drug therapy
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Outpatients
  • Renal Insufficiency / chemically induced*
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Vancomycin / administration & dosage*
  • Vancomycin / adverse effects*

Substances

  • Anti-Bacterial Agents
  • Biomarkers, Pharmacological
  • Vancomycin
  • Creatinine