Top Guns: the Maverick and Goose of Empiric Therapy
Author(s):
Stephen Davies, UVA Health System; Christopher Guidry, UVA Health System; Rhett N. Willis; Zachary Dietch; Puja M. Shah; Robert Sawyer, University of Virginia HSC
Background: Vancomycin and piperacillin-tazobactam (P-T) are commonly used first guns in the empiric management of critically ill patients. Current studies suggest an increased prevalence of acute kidney injury with concomitant use; however, these studies are few and limited by small sample size. The purpose of this study was to compare the prevalence of nephrotoxicity following treatment with vancomycin alone, and concomitant vancomycin and P-T treatment at our institution.
Hypothesis: Concomitant vancomycin and P-T treated patients will experience greater prevalence of nephrotoxicity compared to vancomycin alone-treated patients.
Methods: This was a retrospective cohort of patients treated with vancomycin for Gram positive or mixed infections in our facility from 2005-2009 and not receiving hemodialysis at time of admission. Included patients were stratified by treatment with vancomycin, vancomycin/P-T, or vancomycin/an alternative gram-negative rod (GNR) antibiotic. P-values for categorical variables were computed using Chi-Square while continuous variables were computed using Kruskal-Wallis. Variables deemed statistically significant (<0.0001) were included in the multivariable, log-binomial regression model. Relative risk (RR) and 95% confidence intervals (CI), and P-values were computed using a generalized estimating equation (GEE) approach with robust standard errors (i.e., Huber White “sandwich variance” estimates) to accommodate for a correlated data structure corresponding to multiple episodes of infection per individual.
Results: A total of 530 patients with 1,007 episodes of infection, were treated with vancomycin (150), vancomycin/zosyn (213), or vancomycin/GNR alternative (167). Patient demographics, comorbidities, sites of infection, and organisms of infection were compared between groups. After adjusting for statistically significant variables, vancomycin/P-T (RR=1.08, 95%CI=0.97-1.2; p=0.16) nor vancomycin/GNR alternative (RR=1.08, 95%CI=0.96-1.2; p=0.21) were found to be associated with an increased risk for nephrotoxicity compared with vancomycin alone.
Conclusions: A difference in nephrotoxicity was not observed between vancomycin and vancomycin/P-T-treated patients at our institution. Concomitant use as empiric therapy is appropriate, though larger sample sizes are needed to closely analyze this relationship among “at-risk” subsets of this population.