Background: Recent studies have proposed monitoring vancomycin area under the curve (AUC) as a more precise method of attaining goal exposures compared to trough monitoring. Different dosing methods and different exposure-toxicity thresholds have been proposed. Therefore, we aimed to analyze the relationship between vancomycin AUC and nephrotoxicity reported across recent studies.
Methods: A systematic review of Pubmed, Medline, Scopus and compiled references was conducted. We included randomized, cohorts and case-control studies that reported vancomycin AUCs and risk of nephrotoxicity from (January 1st, 1990 to January 31st, 2018). The primary outcome was nephrotoxicity, defined as an increase in serum creatinine of ≥0.5 mg/liter or a 50% increase from baseline on 2 or more consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Subset analyses were conducted when possible on the impact of AUC0-24hr and AUC24-48hr exposures and AUC versus trough guided dosing on the outcome of nephrotoxicity. AUC nephrotoxicity thresholds ranged between 550-700 mg*hr/L. We grouped values according to lower (i.e, less than 650) or higher average AUC, with a threshold value of >=650 mg*hr/L defining higher AUC based on a recent prospective trial.
Results: We identified 8 eligible observational studies with a total of 2,491 patients. Of those, 5 studies reported AUC0-24 associated with nephrotoxicity, 2 studies reported AUC24-48, and 2 studies reported nephrotoxicity associated with AUC vs. trough-guided dosing. No RCTs were identified. Lower AUC0-24 values were associated with significantly reduced risk of nephrotoxicity (OR 0.36, 95% CI 0.23-0.56). In a sub-analysis of two studies, AUC24-48 <650 mg*h/L was associated with significantly lower risk of nephrotoxicity (OR 0.45, 95% CI 0.27-0.75). Nephrotoxicity associated with AUC-guided dosing was significantly lower than trough-guided dosing (OR 0.68, 95% CI 0.46-0.99).
Conclusion: This meta-analysis suggests that AUC0-24 lower than 650 mg*h/L may result in a decreased risk of nephrotoxicity. AUC guided vancomycin dosing may result in less vancomycin-associated nephrotoxicity. Additional investigations into the benefit of AUC-guided dosing are warranted.
N. J. Rhodes, None
M. Postelnick, None
M. H. Scheetz, None